Psychotherapy focusing on dialogical and narrative perspectives: a systematic review from qualitative and mixed-methods studies.

Introduction: This systematic review identified qualitative and mixed-methods empirical studies on psychotherapy from dialogical and narrative approaches, aiming to address the following questions: (1) How are subjectivity and intersubjectivity qualitatively understood in dialogical and/or narrative psychotherapies studied using dialogical and narrative approaches? (2) How do therapeutic changes occur, including their facilitators and barriers? (3) What psychotherapeutic resources are available for psychotherapists in these types of studies? Method: The articles were selected according to the Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the eligibility criteria proposed by the PICOS strategy (participants, interventions, comparators, outcomes, and study design) from 163 records identified in the Web of Science Core Collection databases. Results: The systematic review process allowed the selection of 16 articles. The results provided insights into the understanding of subjectivity, intersubjectivity, change in psychotherapy, its facilitators, and barriers from these perspectives. It also offered some therapeutic interventions that can be implemented in psychotherapies, integrating dialogical and/or narrative aspects. Discussion: The centrality of dialogical exploration of patient/client resources, therapists as interlocutors fostering client agency, polyphony serving as scaffolding for change, and interconnection with the sociocultural environment are discussed. The integration of this latter topic has been a challenge for these types of studies, considering the active construction of shared meanings. The dialogical and narrative approaches focus psychotherapy on transforming meanings through dialogue and re-authoring stories, evolving within cultural and historical contexts. Thus, this study highlights the relevance of these perspectives in contemporary psychotherapy, emphasizing dialogue in co-creation within an intersubjective framework.

Sentinel lymph node biopsy versus observation in high-risk cutaneous squamous cell carcinoma in immunosuppressed and immunocompetent patients: An inverse probability of treatment weighting study.

BACKGROUND: The survival benefit of sentinel lymph node biopsy (SLNB) in immunocompetent and immunosuppressed patients with high-risk cutaneous squamous cell carcinoma (cSCC) has not been established. OBJECTIVE: To determine whether SLNB improves disease-specific survival (DSS) in high-risk cSCC. Secondary objectives were to analyse disease-free survival, nodal recurrence-free survival and overall survival (OS). METHODS: Multicentre, retrospective, observational cohort study comparing survival outcomes in immunosuppressed and immunocompetent patients treated with SLNB or watchful waiting. Inverse probability of treatment weighting was used to adjust for possible confounding effects. RESULTS: We studied 638 tumours in immunocompetent patients (SLNB n = 42, observation n = 596) and 173 tumours in immunosuppressed patients (SLNB n = 28, observation n = 145). Overall, SLNB was positive in 15.7% of tumours. SLNB was associated with a reduced risk of nodal recurrence (NR) (hazard ratio [HR], 0.05 [95% CI, 0.01-0.43]; p = 0.006), disease specific mortality (HR, 0.17 [95% CI, 0.04-0.72]; p = 0.016) and all-cause mortality (HR, 0.33 [95% CI, 0.15-0.71]; p = 0.004) only in immunocompetent patients. CONCLUSIONS: SLNB was associated with improvements in NR, DSS and OS in immunocompetent but not in immunosuppressed patients with high-risk cSCC.

Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1- stem cell-like T cells over PD-1+ T cells curbing tumor progression.

Introduction: A high frequency of mutations affecting the gene encoding Herpes Virus Entry Mediator (HVEM, TNFRSF14) is a common clinical finding in a wide variety of human tumors, including those of hematological origin. Methods: We have addressed how HVEM expression on A20 leukemia cells influences tumor survival and its involvement in the modulation of the anti-tumor immune responses in a parental into F1 mouse tumor model of hybrid resistance by knocking-out HVEM expression. HVEM WT or HVEM KO leukemia cells were then injected intravenously into semiallogeneic F1 recipients and the extent of tumor dissemination was evaluated. Results: The loss of HVEM expression on A20 leukemia cells led to a significant increase of lymphoid and myeloid tumor cell infiltration curbing tumor progression. NK cells and to a lesser extent NKT cells and monocytes were the predominant innate populations contributing to the global increase of immune infiltrates in HVEM KO tumors compared to that present in HVEM KO tumors. In the overall increase of the adaptive T cell immune infiltrates, the stem cell-like PD-1- T cells progenitors and the effector T cell populations derived from them were more prominently present than terminally differentiated PD-1+ T cells. Conclusions: These results suggest that the PD-1- T cell subpopulation is likely to be a more relevant contributor to tumor rejection than the PD-1+ T cell subpopulation. These findings highlight the role of co-inhibitory signals delivered by HVEM upon engagement of BTLA on T cells and NK cells, placing HVEM/BTLA interaction in the spotlight as a novel immune checkpoint for the reinforcement of the anti-tumor responses in malignancies of hematopoietic origin.

Del Chamanismo al Galenismo: un acercamiento a la curaduría de la nueva sala permanente del museo de la Academia Nacional de Medicina / From Shamanism to Galenism: an approach to the curatorship of the new permanent room of the museum of the National Academy of Medicine

La nueva sala 'Del Chamanismo Al Galenismo' del Museo Ricardo Rueda González inaugurada en noviembre del año 2022, da inicio al museo con el fin de narrar una historia de la medicina desde el contexto local. Aquí se evidencia la experiencia humana compartida del sufrimiento y la esperanza entendidas como enfermedad y tratamiento que fue representada en el mundo prehispánico, durante la colonia y el en siglo XIX.

The new room 'From Shamanism to Galenism' of the Ricardo Rueda González Museum, inaugurated in November 2022, opens the museum with the aim of narrating a history of medicine from the local context. Here the shared human experience of suffering and hope understood as illness and treatment that was represented in the pre-Hispanic world, during the colony and in the 19th century is evidenced.

Glycolysis, monocarboxylate transport, and purinergic signaling are key events in Eimeria bovis-induced NETosis.

The protozoan parasite Eimeria bovis is the causative agent of bovine coccidiosis, an enteric disease of global importance that significantly affects cattle productivity. Previous studies showed that bovine NETosis-an important early host innate effector mechanism of polymorphonuclear neutrophil (PMN)-is elicited by E. bovis stages. So far, the metabolic requirements of E. bovis-triggered NET formation are unknown. We here studied early glycolytic and mitochondrial responses of PMN as well as the role of pH, distinct metabolic pathways, P2 receptor-mediated purinergic signaling, and monocarboxylate transporters 1 and 2 (MCT1, MCT2) in E. bovis sporozoite-induced NET formation. Seahorse-based experiments revealed a rapid induction of both neutrophil oxygen consumption rate (OCR) and early glycolytic responses, thereby reflecting immediate PMN activation and metabolic changes upon confrontation with sporozoites. The impact of these metabolic changes on NET formation was studied via chemical inhibition experiments targeting glycolysis and energy generation by the use of 2-fluor-2-deoxy-D-glucose (FDG), 6-diazo-5-oxo-L-norleucin (DON), sodium dichloroacetate (DCA), oxythiamine (OT), sodium oxamate (OXA), and oligomycin A (OmA) to block glycolysis, glutaminolysis, pyruvate dehydrogenase kinase, pyruvate dehydrogenase, lactate dehydrogenase, and mitochondrial ATP-synthase, respectively. Overall, sporozoite-induced NET formation was significantly diminished via PMN pretreatments with OmA and OXA, thereby indicating a key role of ATP- and lactate-mediated metabolic pathways. Consequently, we additionally studied the effects of extracellular pH, MCT1, MCT2, and purinergic receptor inhibitors (AR-C141900, AR-C155858, theobromine, and NF449, respectively). Pretreatment with the latter inhibitors led to blockage of sporozoite-triggered DNA release from exposed bovine PMN. This report provides first evidence on the pivotal role of carbohydrate-related metabolic pathways and purinergic receptors being involved in E. bovis sporozoite-induced NETosis.

Differential Engraftment of Parental A20 PD-L1 WT and PD-L1 KO Leukemia Cells in Semiallogeneic Recipients in the Context of PD-L1/PD-1 Interaction and NK Cell-Mediated Hybrid Resistance.

The contribution of natural killer (NK) cells to tumor rejection in the context of programmed death-ligand 1/programmed death 1 (PD-L1/PD-1) blockade is a matter of intense debate. To elucidate the role of PD-L1 expression on tumor cells and the functional consequences of engaging PD-1 receptor on cytotoxic cells, PD-L1 expression was genetically inactivated and WT or PD-L1-deficient parental tumor cells were adoptively transferred intravenously into F1 recipients. The engraftment of PD-L1-deficient A20 tumor cells in the spleen and liver of F1 recipients was impaired compared with A20 PD-L1 WT tumor counterparts. To elucidate the mechanism responsible for this differential tumor engraftment and determine the relevance of the role of the PD-L1/PD-1 pathway in the interplay of tumor cells/NK cells, a short-term competitive tumor implantation assay in the peritoneal cavity of semiallogeneic F1 recipients was designed. The results presented herein showed that NK cells killed target tumor cells with similar efficiency regardless of PD-L1 expression, whereas PD-L1 expression on A20 tumor cells conferred significant tumor protection against rejection by CD8 T cells confirming the role of the co-inhibitory receptor PD-1 in the modulation of their cytotoxic activity. In summary, PD-L1 expression on A20 leukemia tumor cells modulates CD8 T-cell-mediated responses to tumor-specific antigens but does not contribute to inhibit NK cell-mediated hybrid resistance, which correlates with the inability to detect PD-1 expression on NK cells neither under steady-state conditions nor under inflammatory conditions.

The impact of CD160 deficiency on alloreactive CD8 T cell responses and allograft rejection.

CD160 is a member of the immunoglobulin superfamily with a pattern of expression mainly restricted to cytotoxic cells. To assess the functional relevance of the HVEM/CD160 signaling pathway in allogeneic cytotoxic responses, exon 2 of the CD160 gene was targeted by CRISPR/Cas9 to generate CD160 deficient mice. Next, we evaluated the impact of CD160 deficiency in the course of an alloreactive response. To that aim, parental donor WT (wild-type) or CD160 KO (knock-out) T cells were adoptively transferred into non-irradiated semiallogeneic F1 recipients, in which donor alloreactive CD160 KO CD4 T cells and CD8 T cells clonally expanded less vigorously than in WT T cell counterparts. This differential proliferative response rate at the early phase of T cell expansion influenced the course of CD8 T cell differentiation and the composition of the effector T cell pool that led to a significant decreased of the memory precursor effector cells (MPECs) / short-lived effector cells (SLECs) ratio in CD160 KO CD8 T cells compared to WT CD8 T cells. Despite these differences in T cell proliferation and differentiation, allogeneic MHC class I mismatched (bm1) skin allograft survival in CD160 KO recipients was comparable to that of WT recipients. However, the administration of CTLA-4.Ig showed an enhanced survival trend of bm1 skin allografts in CD160 KO with respect to WT recipients. Finally, CD160 deficient NK cells were as proficient as CD160 WT NK cells in rejecting allogeneic cellular allografts or MHC class I deficient tumor cells. CD160 may represent a CD28 alternative costimulatory molecule for the modulation of allogeneic CD8 T cell responses either in combination with costimulation blockade or by direct targeting of alloreactive CD8 T cells that upregulate CD160 expression in response to alloantigen stimulation.

Copper and Copper/Zinc Ratio in a Series of Cystic Fibrosis Patients.

Cystic fibrosis (CF) patients require a stable and sufficient supply of micronutrients. Since copper is an essential micronutrient for human development, a cross-sectional study was carried out to investigate the serum copper levels, serum copper/zinc (Cu/Zn) ratios, and their relationship with nutritional indicators in a group of CF patients. Anthropometric, biochemical, and dietary measurements, an abdominal ultrasound, and respiratory and pancreatic tests were conducted. Seventeen CF patients were studied (10 females, 59%), 76.5% of whom were ∆F580. Their mean serum copper (113 ± 23 µg/dL) was normal, and there was only one teenager with hypocupremia (6%) and two children with hypercupremia (18%). A significant association between serum copper and zinc levels was discovered. The Cu/Zn ratio was higher than 1.00 for 94% of patients, which is an indicator of an inflammation status. There was no significant correlation between the serum copper concentrations and respiratory and pancreatic function, respiratory colonization, and the results of the abdominal ultrasound. Linear regression analysis showed that serum copper had a positive association with both the Z-score body mass index (BMI) and mean bone conduction speed (BCS). Therefore, since 94% of CF patients had a Cu/Zn ratio > 1.00, this factor must alert us to consider the risk of zinc deficiency and high inflammatory response. The measurement of serum zinc alone does not show one's zinc status. However, the Cu/Zn ratio may be an indicator of zinc deficiency and the inflammatory status of CF patients.

The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens.

Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR.

Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for effective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model.

The expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrated that dual blockade of PD-L1 interaction with PD-1 and CD80 enhanced anti-tumor immune responses that either delayed tumor growth or led to its complete eradication. PD-L1 expression on non-tumor cells of the tumor microenvironment was required for the promotion of tumor immune escape and its blockade elicited potent anti-tumor responses to PD-L1 WT and to PD-L1-deficient tumor cells. PD-L1+ tumors implanted in PD-L1-deficient mice exhibited delayed tumor growth independently of PD-L1 blockade. These findings emphasize that PD-L1 expression on non-tumor cells plays a major role in this tumor model. These observations should turn our attention to the tumor microenvironment in hematological malignancies because of its unappreciated contribution to create a conditioned niche for the tumor to grow and evade the anti-tumor immune response.

When to assess the DIEP flap perfusion by intraoperative indocyanine green angiography in breast reconstruction?

BACKGROUND: Although the indocyanine green angiography (ICGA) has been used for years in the assessment of Deep Inferior Epigastric Perforator (DIEP) perfusion, it has not yet been established when it should be performed during the surgery. The aim of this study is to evaluate whether it is better to perform the test on the donor or recipient sites. METHODS: Intraoperative perfusion of 46 DIEP flaps was assessed twice, on the donor and recipient sites. Differences between both ischemic areas of each flap were statistically analyzed. In addition, perforator location and risk factors were evaluated in order to assess whether they are associated with changes in the perfusion of the flap between both sites. RESULTS: Differences between ischemic areas on the donor and recipient sites were statistically significant (p = 0.012). However, in most cases (82.6%) the ischemic area was the same on both sites, and the final flap design only changed in two cases (4.3%) because of the ICGA findings on the recipient site. Besides, performing the ICGA on the donor site facilitated the identification of the best perfused areas, allowed a better planning of its placement into the recipient site, and also can be useful to choose the best perforator. Bilateral DIEP flap, lateral location of the perforator and tobacco use had a statistically significant association with lower probability to increase the perfusion area between both sites. CONCLUSIONS: several advantages have been found in performing the ICGA on the donor site to assess the perfusion of the DIEP flap.

CD160 serves as a negative regulator of NKT cells in acute hepatic injury.

CD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160-/- mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160-/- mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160-/- mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160-/- mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activation.

Zinc Nutritional Status in Patients with Cystic Fibrosis.

BACKGROUND: Zinc is an essential nutrient for all forms of life and its deficiency affects the normal growth and development of human beings. OBJECTIVE: The main aim was to investigate zinc nutritional status by serum zinc concentration (SZC) and dietary zinc intake and their association in cystic fibrosis (CF) patients. METHODS: A cross-sectional study was conducted in CF patients. Anthropometric measurements and respiratory and pancreatic tests were conducted. Hypozincemia was determined by SZC while using atomic absorption spectrophotometry and dietary zinc deficiency by prospective 72-h dietary surveys. RESULTS: Mean SZC (87.2 ± 16.7 µg/dL) and dietary zinc intake (97 ± 26.9% Dietary Reference Intake) were normal. Three of 17 patients with CF (17.6%) had hypozincemia and four (23.5%) had a dietary zinc deficiency. No patient with dietary zinc deficiency had hypozincemia. A positive and significant association was observed between SZC and Z-score of BMI-for-age (p = 0.048) and weight-for-height (p = 0.012) and between dietary zinc intake and energy intake (EI, p = 0.036) and Z-score of weight-for-high (p = 0.029). CONCLUSION: SZC was associated with the nutritional status, expressed as BMI (Body Mass Index) and weight-for-height Z score, and dietary zinc intake with EI and weight-for-height Z-score. No patient with hypozincemia had dietary zinc deficiency. This situation should alert us to a marginal zinc deficiency and it may explain why there were no overlapping cases between the two groups. We suggest that probably 41% of the cases in this study would be at elevated risk of zinc deficiency and a zinc supplementation may be considered.

Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma.

Natural Killer T cells (NKT cells) are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.

Laparoscopic transgastric ERCP in bariatric surgery patients: our experience.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the surgical treatment of choice for morbid obesity. Several therapeutic options to remove common bile duct (CBD) stones have been proposed in these patients. Laparoscopy-assisted transgastric ERCP (LATERCP) has a high success rate. However, the procedure is not fully standardized and some technical variations have been proposed. We introduce two cases in which laparoscopic transgastric ERCP has been used to treat choledocholithiasis after LRYGB.

Enteroparasitoses and Toxocarosis Affecting Children from Mar del Plata City, Argentina.

This study evaluated the existence of enteroparasitoses and toxocarosis in children of peripheral (PC) and urban communities (UC) from Mar del Plata city (Argentina) and their associations with socio-environmental conditions. A Parasite Vulnerability Index (PVI) was elaborated using variables such as overcrowding, floor type, drinking water source, wastewater disposal, solid waste disposal, presence of animals and schooling level. The PC evidenced statistically significant higher frequencies of families with high (38.9%) and medium (55.5%) PVI, while in the UC low PVI (93%) was the most frequent. A statistically significant higher frequency of PC children was parasitized (30.2 vs. 14.5%; χ 2 Pearson = 5.21; P < 0.05), presented higher parasite frequencies, specific richness, parasitic loads, and they also evidenced polyparasitism. The Multiple Correspondence Analysis (MCA) showed associations between PC-parasitized children, overcrowding and contact with pets and farm animals. The ELISA test to the specified determination of Toxocara canis IgG was reactive in a statistically significant higher proportion of PC children than the UC (55 vs. 8.5%; χ 2 = 30.5; P < 0.01). The MCA associated PC reactive children, not adequate hand washing, moderate and hypereosinophilia and contact with pets and farm animals. Deficient socio-environmental conditions became children more vulnerable to get enteroparasitoses and toxocarosis in the PC than in the UC.

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway.

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator (HVEM/BTLA) signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper (Tfh) cells (B220-, CD4+ CXCR5+ PD-1high), extrafollicular helper cells (B220-, CD4+ CXCR5- PD-1+ and PD-1-) and germinal centre (GC) B cells (B220+Fas+ GL7+) were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

Modulation of cytotoxic responses by targeting CD160 prolongs skin graft survival across major histocompatibility class I barrier.

CD160 is a glycosylphosphatidylinositol-anchored protein of the immunoglobulin superfamily. It exhibits a pattern of expression coincident in humans and mice that is mainly restricted to cytotoxic cells and to all intestinal intraepithelial T lymphocytes. B- and T-lymphocyte attenuator (BTLA) and CD160 interact with cysteine-rich domain 1 of the extracellular region of Herpesvirus entry mediator (HVEM). CD160 engagement by HVEM can deliver inhibitory signals to a small subset of human CD4 T cells and attenuate its proliferation and cytokine secretion, but can also costimulate natural killer cells or intraepithelial lymphocytes. In turn, CD160 and BTLA can also function as agonist ligands being capable of costimulating T cells through membrane HVEM. Based on the restricted pattern of CD160 expression in cytotoxic cells, we postulated that CD160 may represent a suitable target for immune intervention in the setting of transplantation to modulate allogeneic cytotoxic responses. We demonstrated that in vivo administration of anti-CD160 antibody in combination with anti-CD40 L antibody to limit CD4 T-cell help modulated cytotoxic responses in a major histocompatibility complex class I mismatched model of allogeneic skin graft transplantation (bm1 donor to C57BL/6 recipient) and significantly prolonged graft survival. The implementation of this strategy in transplantation may reinforce current immunosuppression protocols and contribute to a better control of CD8 T-cell responses.