Dynamic imaging of force chains in 3D granular media.

Granular media constitute the most abundant form of solid matter on Earth and beyond. When external forces are applied to a granular medium, the forces are transmitted through it via chains of contacts among grains-force chains. Understanding the spatial structure and temporal evolution of force chains constitutes a fundamental goal of granular mechanics. Here, we introduce an experimental technique, interference optical projection tomography, to study force chains in three-dimensional (3D) granular packs under triaxial shear loads and illustrate the technique with random assemblies of spheres and icosahedra. We find that, in response to an increasing vertical load, the pack of spheres forms intensifying vertical force chains, while the pack of icosahedra forms more interconnected force-chain networks. This provides microscopic insights into why particles with more angularity are more resistant to shear failure-the interconnected force-chain network is stronger (that is, more resilient to topological collapse) than the isolated force chains in round particles. The longer force chains with less branching in the pack of round particles are more likely to buckle, which leads to the macroscopic failure of the pack. This work paves the way for understanding the grain-scale underpinning of localized failure of 3D granular media, such as shear localization in landslides and stick-slip frictional motion in tectonic and induced earthquakes.

The yielding of granular matter is marginally stable and critical.

Amorphous materials undergo a transition from liquid-like to solid-like states through processes like rapid quenching or densification. Under external loads, they exhibit yielding, with minimal structural changes compared to crystals. However, these universal characteristics are rarely explored comprehensively in a single granular experiment due to the added complexity of inherent friction. The discernible differences between static configurations before and after yielding are largely unaddressed, and a comprehensive examination from both statistical physics and mechanical perspectives is lacking. To address these gaps, we conducted experiments using photoelastic disks, simultaneously tracking particles and measuring forces. Our findings reveal that the yielding transition demonstrates critical behavior from a statistical physics standpoint and marginal stability from a mechanical perspective, akin to the isotropic jamming transition. This criticality differs significantly from spinodal criticality in frictionless amorphous solids, highlighting unique characteristics of granular yielding. Furthermore, our analysis confirms the marginal stability of granular yielding by assessing the contact number and evaluating the balance between weak forces and small gaps. These factors serve as structural indicators for configurations before and after yielding. Our results not only contribute to advancing our understanding of the fundamental physics of granular materials but also bear significant implications for practical applications in various fields.

Elasticity and rheology of auxetic granular metamaterials.

The flowing, jamming, and avalanche behavior of granular materials is satisfyingly universal and vexingly hard to tune: A granular flow is typically intermittent and will irremediably jam if too confined. Here, we show that granular metamaterials made from particles with a negative Poisson's ratio yield more easily and flow more smoothly than ordinary granular materials. We first create a collection of auxetic grains based on a re-entrant mechanism and show that each grain exhibits a negative Poisson's ratio regardless of the direction of compression. Interestingly, we find that the elastic and yielding properties are governed by the high compressibility of granular metamaterials: At a given confinement, they exhibit lower shear modulus, lower yield stress, and more frequent, smaller avalanches than materials made from ordinary grains. We further demonstrate that granular metamaterials promote flow in more complex confined geometries, such as intruder and hopper geometries, even when the packing contains only a fraction of auxetic grains. Moreover, auxetic granular metamaterials exhibit enhanced impact absorption. Our findings blur the boundary between complex fluids and metamaterials and could help in scenarios that involve process, transport, and reconfiguration of granular materials.

Underexcitation prevents crystallization of granular assemblies subjected to high-frequency vibration.

Crystallization of dry particle assemblies via imposed vibrations is a scalable route to assemble micro/macro crystals. It is well understood that there exists an optimal frequency to maximize crystallization with broad acceptance that this optimal frequency emerges because high-frequency vibration results in overexcitation of the assembly. Using measurements that include interrupted X-ray computed tomography and high-speed photography combined with discrete-element simulations we show that, rather counterintuitively, high-frequency vibration underexcites the assembly. The large accelerations imposed by high-frequency vibrations create a fluidized boundary layer that prevents momentum transfer into the bulk of the granular assembly. This results in particle underexcitation which inhibits the rearrangements required for crystallization. This clear understanding of the mechanisms has allowed the development of a simple concept to inhibit fluidization which thereby allows crystallization under high-frequency vibrations.

Granular crystals as strong and fully dense architectured materials.

Dense topologically interlocked panels are made of well-ordered, stiff building blocks interacting mainly by frictional contact. Under mechanical loads, the deformation of the individual blocks is small, but they can slide and rotate collectively, generating high strength, toughness, impact resistance, and damage tolerance. Here, we expand this construction strategy to fully dense, 3D architectured materials made of space filling building blocks or "grains." We used mechanical vibrations to assemble 3D printed rhombic dodecahedral and truncated octahedral grains into fully dense face-centered cubic and body-centered cubic "granular crystals." Triaxial compression tests revealed that these granular crystals are up to 25 times stronger than randomly packed spheres and that after testing, the grains can be recycled into new samples with no loss of strength. They also displayed a rich set of mechanisms: nonlinear deformations, crystal plasticity reminiscent of atomistic mechanisms, geometrical hardening, cross-slip, shear-induced dilatancy, and microbuckling. A most intriguing mechanism involved a pressure-dependent "granular crystal plasticity" with interlocked slip planes that completely forbid slip along certain loading directions. We captured these phenomena using a three-length scale theoretical model which agreed well with the experiments. Once fully understood and harnessed, we envision that these mechanisms will lead to 3D architectured materials with unusual and attractive combinations of mechanical performances as well as capabilities for repair, reshaping, on-site alterations, and recycling of the building blocks. In addition, these granular crystals could serve as "model materials" to explore unusual atomic scale deformation mechanisms, for example, non-Schmid plasticity.

Mechanistic framework for reduced-order models in soft materials: Application to three-dimensional granular intrusion.

Soft materials often display complex behaviors that transition through apparent solid- and fluid-like regimes. While a growing number of microscale simulation methods exist for these materials, reduced-order models that encapsulate the macroscale physics are often desired to predict how external bodies interact with soft media. Such an approach could provide direct insights in diverse situations from impact and penetration problems to locomotion over natural terrains. This work proposes a systematic program to develop three-dimensional (3D) reduced-order models for soft materials from a fundamental basis using continuum symmetries and rheological principles. In particular, we derive a reduced-order, 3D resistive force theory (3D-RFT), which is capable of accurately and quickly predicting the resistive stress distribution on arbitrary-shaped bodies intruding through granular media. Aided by a continuum description of the granular medium, a comprehensive set of spatial symmetry constraints, and a limited amount of reference data, we develop a self-consistent and accurate 3D-RFT. We verify the model capabilities in a wide range of cases and show that it can be quickly recalibrated to different media and intruder surface types. The premises leading to 3D-RFT anticipate application to other soft materials with strongly hyperlocalized intrusion behavior.

High time-resolved studies of stick-slip show similar dilatancy to fast and slow earthquakes.

Fast and slow earthquakes are two modes of energy release by the slip in tectonic fault rupture. Although fast and slow slips were observed in the laboratory stick-slip experiments, due to the sampling rate limitation, the details of the fault thickness variation were poorly understood. Especially, why a single fault would show different modes of slip remains elusive. Herein, we report on ring shear experiments with an ultrahigh sampling rate (10 MHz) that illuminate the different physical processes between fast and slow slip events. We show that the duration of slips ranged from dozens to hundreds of milliseconds. Fast slip events are characterized by continuous large-amplitude AE (acoustic emission) and somewhat intricate variation of the sample thickness: A short compaction pulse during the rapid release of stress is followed by dilation and vibrations of the sample thickness. As the slip ends, the thickness of the sample first recovers by slow compaction and then dilates again before nucleation of the following slip event. In contrast, during slow slip events, the shear stress reduction is accompanied by intermittent bursts of low-amplitude AE and sample dilation. We observed the detailed thickness variation during slips and found that dilation occurs during both fast and slow slips, which is consistent with natural observations of coseismic dilatation. This study may be used to reveal the mechanism of fault slips during fast and slow earthquakes, which explain the potential effect of fast and slow slips on stress redistribution and structural rearrangement in faults.

Assessing continuum plasticity postulates with grain stress and local strain measurements in triaxially compressed sand.

Critical state and continuum plasticity theories have been used in research and engineering practice in soil and rock mechanics for decades. These theories rely on postulated relationships between material stresses and strains. Some classical postulates include coaxiality between stress and strain rates, stress-dilatancy relationships, and kinematic assumptions in shear bands. Although numerical and experimental data have quantified the strains and grain kinematics in such experiments, little data quantifying grain stresses are available. Here, we report the first-known grain stress and local strain measurements in triaxial compression tests on synthetic quartz sands using synchrotron X-ray tomography and 3D X-ray diffraction. We use these data to examine the micromechanics of shear banding, with a focus on coaxiality, stress-dilatancy, and kinematics within bands. Our results indicate the following: 1) elevated deviatoric stress, strain, and stress ratios in shear bands throughout experiments; 2) coaxial principal compressive stresses and strains throughout samples; 3) significant contraction along shear bands; 4) vanishing volumetric strain but nonvanishing stress fluctuations throughout samples at all stages of deformation. Our results provide some of the first-known in situ stress and strain measurements able to aid in critically evaluating postulates employed in continuum plasticity and strain localization theories for sands.

X-ray 3D imaging-based microunderstanding of granular mixtures: Stiffness enhancement by adding small fractions of soft particles.

This research focuses on performing ultrasound propagation measurements and micro-X-ray computed tomography (µXRCT) imaging on prestressed granular packings prepared with biphasic mixtures of monodisperse glass and rubber particles at different compositions/fractions. Ultrasound experiments employing piezoelectric transducers, mounted in an oedometric cell (complementing earlier triaxial cell experiments), are used to excite and detect longitudinal ultrasound waves through randomly prepared mixtures of monodisperse stiff/soft particles. While the fraction of the soft particles is increasing linearly from zero, the effective macroscopic stiffness of the granular packings transits nonlinearly and nonmonotonically toward the soft limit, remarkably via an interesting stiffer regime for small rubber fractions between 0.1 ≲ ν ≲ 0.2. The contact network of dense packings, as accessed from µXRCT, plays a key role in understanding this phenomenon, considering the structure of the network, the chain length, the grain contacts, and the particle coordination. While the maximum stiffness is due to surprisingly shortened chains, the sudden drop in elastic stiffness of the mixture packings, at ν ≈ 0.4, is associated with chains of particles that include both glass and rubber particles (soft chains); for ν ≲ 0.3, the dominant chains include only glass particles (hard chains). At the drop, ν ≈ 0.4, the coordination number of glass and rubber networks is approximately four and three, respectively, i.e., neither of the networks are jammed, and the chains need to include particles from another species to propagate information.

Unique Viscoelasticity and Hierarchical Relaxation Dynamics of Molecular Granular Materials.

Resulting from the dense packing of subnanometer molecular clusters, molecular granular materials (MGMs) are shown to maintain high elasticity far above their apparent glass transition temperature (Tg*). However, our microscopic understanding of their structure-property relationship is still poor. Herein, 1 nm polyhedral oligomeric silsesquioxanes (POSSs) are appended to a backbone chain in a brush configuration with different flexible linker chains. Assemblies of these brush polymers exhibit hierarchical relaxation dynamics with the glass transition arising from the cooperative dynamics of packed POSSs. The interaction among the assemblies can be strengthened by increasing the rigidity of linkers with the MGM relaxation modes changing from colloid- to polymer chain-like behavior, rendering their tunable viscoelasticity. This finally contributes to the decoupling of mechanical and thermal properties by showing elasticity dominant mechanical properties at a temperature 150 K above the Tg*.

High-performance internal circulation anaerobic granular sludge reactor for cattle slaughterhouse wastewater treatment and simultaneous biogas production.

This research investigates the efficacy of a high-performance pilot-scale Internal Circulation Anaerobic Reactor inoculated with Granular Sludge (ICAGSR) for treating cattle slaughterhouse wastewater while concurrently generating biogas. The primary objective is to assess the efficiency and performance of ICAGSR in terms of organic pollutant removal and biogas production using granular anaerobic sludge. The research methodology entails operating the ICAGSR system under ambient conditions and systematically varying key parameters, including different Hydraulic Retention Times (HRTs) (24, 12, and 8 h) and Organic Loading Rates (OLRs) (3.3, 6.14, and 12.83 kg COD/m³. d). The study focuses on evaluating pollutants' removal and biogas production rates. Results reveal that the ICAGSR system achieves exceptional removal efficiency for organic pollutants, with Chemical Oxygen Demand (COD) removal exceeding 74%, 67%, and 68% at HRTs of 24, 12, and 8 h, respectively. Furthermore, the system demonstrates stable and sustainable biogas production, maintaining average methane contents of 80%, 76%, and 72% throughout the experimental period. The successful operation of the ICAGSR system underscores its potential as a viable technology for treating cattle slaughterhouse wastewater and generating renewable biogas. In conclusion, this study contributes to wastewater treatment and renewable energy production by providing a comprehensive analysis of the ICAGSR system's hydrodynamic properties. The research enhances our understanding of the system's performance optimization under varying conditions, emphasizing the benefits of utilizing ICAGSR reactors with granular sludge as an effective and sustainable approach. Identifying current gaps, future research directions aim to further refine and broaden the application of ICAGSR technology in wastewater treatment and renewable energy initiatives.

Accelerating Patterned Vascularization Using Granular Hydrogel Scaffolds and Surgical Micropuncture.

Bulk hydrogel scaffolds are common in reconstructive surgery. They allow for the staged repair of soft tissue loss by providing a base for revascularization. Unfortunately, they are limited by both slow and random vascularization, which may manifest as treatment failure or suboptimal repair. Rapidly inducing patterned vascularization within biomaterials has profound translational implications for current clinical treatment paradigms and the scaleup of regenerative engineering platforms. To address this long-standing challenge, a novel microsurgical approach and granular hydrogel scaffold (GHS) technology are co-developed to hasten and pattern microvascular network formation. In surgical micropuncture (MP), targeted recipient blood vessels are perforated using a microneedle to accelerate cell extravasation and angiogenic outgrowth. By combining MP with an adjacent GHS with precisely tailored void space architecture, microvascular pattern formation as assessed by density, diameter, length, and intercapillary distance is rapidly guided. This work opens new translational opportunities for microvascular engineering, advancing reconstructive surgery, and regenerative medicine.

Nondestructive and three-dimensional visualization by identifying elements using synchrotron radiation microscale X-ray CT reveals microbial and cavity distributions in anaerobic granular sludge.

We developed a nondestructive three-dimensional microbial visualization method utilizing synchrotron radiation X-ray microscale computed tomography to better understand the relationship between microorganisms and their surrounding habitats. The method was tested and optimized using a mixture of axenic Escherichia coli and Comamonas testosteroni. The osmium-thiocarbohydrazide-osmium method was used to stain all the microbial cells, and gold in situ hybridization was used to detect specific phylogenetic microbial groups. The stained samples were embedded in epoxy resin for microtomographic analysis. Differences in X-ray absorbances were calculated by subtracting the pre-L3-edge images from the post-L3-edge images to visualize the osmium and gold signals. Although we successfully detected cells stained with osmium, those labeled with gold were not detected, probably because of the insufficient density of gold atoms in the microbial cells. We then applied the developed technique to anaerobic granules and visualized the distribution of microbial cells and extracellular polymeric substances. Empty spaces were highlighted to determine the cavity distribution in granules. Numerous independent cavities of different sizes were identified in the granules. The developed method can be applied to various environmental samples for deeper insights into microbial life in their habitats. IMPORTANCE: Microorganisms inhabit diverse environments and often form biofilms. One factor that affects their community structure is the surrounding physical environment. The arrangement of residential space within the formed biofilm plays a crucial role in the supply and transportation of substances, as well as the discharge of metabolites. Conventional approaches, such as scanning electron microscopy and confocal laser scanning microscopy combined with fluorescence in situ hybridization, have limitations as they provide information primarily from the biofilm surface and cross-sections. In this study, we developed a method for detecting microorganisms in biofilms using synchrotron radiation X-ray microscale computer tomography. The developed method allows nondestructive three-dimensional observation of biofilms at a single-cell resolution (voxel size of approximately 200 nm), facilitating an understanding of the relationship between microorganisms and their physical habitats.

Tlx1 regulates acinar and duct development in mouse salivary glands.

Tlx1 encodes a transcription factor expressed in several craniofacial structures of developing mice. The role of Tlx1 in salivary gland development was examined using morphological and immunohistochemical analyses of Tlx1 null mice. Tlx1 is expressed in submandibular and sublingual glands but not parotid glands of neonatal and adult male and female C57Bl/6J (Tlx1+/+ ) mice. TLX1 protein was localized to the nuclei of terminal tubule cells, developing duct cells and mesenchymal cells in neonatal submandibular and sublingual glands, and to nuclei of duct cells and connective tissue cells in adult glands. Occasionally, TLX1 was observed in nuclei of epithelial cells in or adjacent to the acini. Submandibular glands were smaller and sublingual glands were larger in size in mutant mice (Tlx1-/- ) compared to wild-type mice. Differentiation of terminal tubule and proacinar cells of neonatal Tlx1-/- submandibular glands was abnormal; expression of their characteristic products, submandibular gland protein C and parotid secretory protein, respectively, was reduced. At 3 weeks postnatally, terminal tubule cells at the acinar-intercalated duct junction were poorly developed or absent in Tlx1-/- mice. Granular convoluted ducts in adult mutant mice were decreased, and epidermal growth factor and nerve growth factor expression were reduced. Along with normal acinar cell proteins, adult acinar cells of Tlx1-/- mice continued to express neonatal proteins and expressed parotid proteins not normally present in submandibular glands. Sublingual gland mucous acinar and serous demilune cell differentiation were altered. Tlx1 is necessary for proper differentiation of submandibular and sublingual gland acinar cells, and granular convoluted ducts. The mechanism(s) underlying Tlx1 regulation of salivary gland development and differentiation remains unknown.

TOX as a new diagnostic marker for T cell large granular lymphocytic leukaemia.

AIMS: T cell large granular lymphocytic leukaemia (T-LGLL) is a rare disorder that may underlie otherwise unexplained cytopenias. The identification of T-LGLL cells in bone marrow biopsies can be a challenge, because a robust immunohistochemistry marker is lacking. The markers currently in use (granzyme B, TIA-1 and CD8) are difficult to interpret or lack specificity. Therefore, we investigated whether immunohistochemistry for thymocyte selection-associated high-mobility group box (TOX), a transcription factor that associates with chronic T cell stimulation, could be a reliable tool for the identification of T-LGLL cells. METHODS AND RESULTS: In this retrospective study, expression of TOX in CD8+ cells in bone marrow biopsies of T-LGLL patients (n = 38) was investigated and compared to bone marrow of controls with reactive T cell lymphocytosis (n = 10). All biopsies were evaluated for TOX staining within the CD8-positive T cell population. The controls were essentially negative for TOX, whereas all T-LGLL cases were positive (median = 80%, range = 10-100%), even when bone marrow involvement was subtle. CONCLUSION: TOX is a highly sensitive marker for the neoplastic cells of T-LGLL and we recommend its use, especially in the diagnostic work-up of patients with unexplained cytopenias.

Iron inhibits glioblastoma cell migration and polarization.

Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate-a key question, especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.

Clinical characteristics and treatment outcomes of Asian patients with T-cell large granular lymphocytic Leukemia: a single-center analysis of 67 cases.

Large granular lymphocytic (LGL) leukemia is a clonal lymphoproliferative disorder of LGLs derived from cytotoxic T lymphocytes or natural killer cells. However, the clinical features and treatment responses are still not fully understood because of the rarity of the disease. To describe and assess a cohort of patients with T-cell large granular lymphocytic leukemia (T-LGLL). Single-center, retrospective, observational study. We retrospectively collected the clinical data of patients diagnosed with T-LGLL at Seoul National University Hospital since 2006. We included 67 patients in this study. The median age at diagnosis was 60 years. Additionally, 37 patients (55%) were symptomatic, and 25 (37%) had splenomegaly; 54 patients (81%) required treatment. Cyclophosphamide (n = 35), methotrexate (n = 25), and cyclosporin A (n = 19) were used most frequently for treatment, and their overall response rates were similar: cyclophosphamide (77%), methotrexate (64%), and cyclosporin A (63%). Splenomegaly was associated with an increased response rate to first-line therapy and a decreased complete response rate. Thrombocytopenia was associated with decreased response rates to cyclophosphamide, methotrexate, cyclosporin A, and steroids. In contrast, a high LGL number (> 2000/µL) in the peripheral blood smear was associated with increased response rates to cyclophosphamide, methotrexate, cyclosporin A, and steroids. This study describes the clinical features and treatment outcomes of patients with T-LGLL, providing valuable information for clinical decision-making regarding T-LGLL treatment.

T-large granular lymphocyte frequencies and correlates in disease states detected by multiparameter flow cytometry in pediatric and young adult population.

T-large granular lymphocytes (T-LGL) characterized by dim CD5 staining, although not completely understood, have unique roles in the immune system. Expansion of peripheral blood (PB) clonal T-LGL populations is associated with various entities in adults. We have previously demonstrated clonal T-LGL proliferations in pediatric immune dysregulation/inflammatory/proliferative conditions. However, T-LGL populations have not been studied in broader spectrum pathologies. In this study we evaluated sizes and correlates of T-LGL populations in the pediatric and young adult populations with various disease states. Lymphocytes including T-LGL were investigated retrospectively by reviewing PB multiparameter flow cytometric data with various indications over a 4-year period. Associations with clinical, laboratory findings, and T-LGL population sizes were sought. Among 520 cases reviewed, 240 were females and 280 males with a mean age of 9 years (0-33 years); mean T-LGL population constituted 14% (1-67%) in PB T cells. There were significant differences between T-LGL and CD5-bright, regular T cells. T-LGL correlated with CD8 + /DR + (R = 0.570; P < 0.01) and CD8 + /CD11b + (R = 0.597; P < 0.01) expression, indicating activated cytotoxic phenotype. The highest average T-LGL were seen in bone marrow transplant recipients (23.7%), Evans syndrome (23.7%), lymphoma (20.6%), and acute EBV infection (20.4%) cases, all with underlying immune dysregulation pathologies. In pediatric and young adult patients with different clinical conditions, PB T-LGL constitute an average of 14% of the T cells and have a predominantly activated cytotoxic T cell phenotype. Higher relative presence was seen in cases with an immune dysregulation background. These results may serve as a reference for T-LGL research efforts.

Refractory pure red cell aplasia associated with T-cell large granular lymphocyte leukemia treated by ruxolitinib.

Acquired pure red cell aplasia (PRCA) is a rare syndrome characterized by normocytic normochromic anemia with severe reticulocytopenia and absence of erythroid precursors in the bone marrow. For refractory PRCA patients, the low response rate and high toxicity of alternative therapies pose a great challenge. T-cell large granular lymphocyte (T-LGL) leukemia is one of the most common conditions in secondary PRCA and also the most difficult form to manage with an inferior treatment response to other secondary PRCA forms. T-LGL leukemia exhibits sustained activation of the intracellular JAK-STAT signaling pathway. We herein report a case of PRCA associated with T-LGL leukemia that had been refractory to multiple lines of therapies and was successfully treated by ruxolitinib. The patient achieved complete remission and tolerated ruxolitinib well without occurrence of neutropenia or thrombocytopenia. This preliminary finding favors ruxolitinib as a potential salvage therapy for refractory PRCA associated with T-LGL leukemia.

Characteristics of large granular lymphocyte leukemia associated with variable common immunodeficiency disorders: A study of 12 cases.

OBJECTIVES: Common Variable Immunodeficiency Disorders (CVID) and Large Granular Lymphocytes leukemia (LGLL) exhibit diverse clinical manifestations including infections, dysimmunity, and lymphoproliferation. Recent decades have seen the discovery of new genes in the lymphopoiesis pathway, such as JAK-STAT. This case series supplemented by a literature review aims to describe clinical and biological characteristics of patients with both CIVD and LGLL. METHODOLOGY: Patients were included through a call for comments to French and Belgian centers and through a literature review via PubMed. Clinical characteristics were compared to two large French cohort involving CVID and LGLL patients. RESULTS: Twelve patients were included. In all cases, CVID precedes LLGL (median diagnosis delay for LLGL was 7 years). Most cases presented with splenomegaly and autoimmune cytopenia. Ten out of 12 patients underwent splenectomy during follow up. CONCLUSIONS: Patients with LGLL and CVID differ from patients without immune deficiency in term of clinical presentation and prognosis. We suggest CVID may act as a trigger of LGL lymphocytosis, due to endogenous and exogenous antigenic pressure leading to the selection of a dominant LGL clone and stimulation of the JAK-STAT pathway. The role of splenomegaly and splenectomy in LGLL onset warrant further investigation in future studies.