Tuberculosis cutánea esporotricoide en la Amazonía peruana: reporte de caso / Sporotrichoid cutaneous tuberculosis in the peruvian amazon: case report

RESUMEN La tuberculosis cutánea es una presentación rara de la infección por Mycobacterium tuberculosis. Se presenta el caso de una mujer sin antecedentes médicos de importancia, con un tiempo de enfermedad de año y medio, caracterizado por lesiones tipo esporotricoide, con diseminación linfocutánea en miembro superior derecho, de evolución lentamente progresiva. Se realizó un estudio histopatológico encontrándose células gigantes tipo Langhans y escasa necrosis. El paciente recibió terapia de esquema sensible antituberculoso, con evolución favorable.

ABSTRACT Cutaneous tuberculosis is a rare presentation of Mycobacterium tuberculosis infection. We present the case of a woman without important medical history, with a disease period of one year and a half, characterized by sporotrichoid-like lesions, with lymphocutaneous dissemination in the right upper limb, and with slowly progressive evolution. The histopathological tests revealed Langhans type giant cells and scarce necrosis. The patient received therapy with a sensitive antituberculous scheme, and evolved favorably.

Granulomas en dermatopatología: principales entidades. Parte I / Granulomas in Dermatopathology: Principal Diagnoses - Part 1

En esta serie de 2 artículos realizamos una revisión de las principales entidades dermatopatológicas que cursan con granulomas. Esta primera parte se ha centrado en la aclaración de los conceptos, la presentación de los tipos de granulomas y de las células gigantes, así como en entidades muy diversas de origen no infeccioso. Algunas de ellas de origen metabólico, como la necrobiosis lipoídica: otras relacionadas con linfomas, como la micosis fungoides granulomatosa, y otras tan extendidas que casi resultan un problema cotidiano en las consultas de dermatología, como la rosácea (AU)

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice (AU)

Granulomas en dermatopatología: principales entidades. Parte II / Granulomas in Dermatopathology: Principal Diagnoses — Part 2

Esta es la segunda parte de una serie dedicada a la patología granulomatosa en la biopsia cutánea. Mientras que en la primera parte hablamos, entre otras, de algunas condiciones metabólicas y tumorales, esta segunda parte abordará fundamentalmente patología infecciosa de diversos tipos, junto con otras condiciones relativamente frecuentes en las consultas de dermatología (AU)

Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists (AU)

Primary pituitary tuberculosis

Tuberculosis is an infectious disease that involves any organ. However, the primary pituitary tuberculosis is an extremely rare disease. Intracranial tuberculomas account for 0.15-5% of intracranial space-occupying lesions, of which, pituitary as the primary site is unusual, and easily misdiagnosed as pituitary adenoma. In this setting, the late diagnosis can result in permanent endocrine dysfunction. We report the case of a 50-year-old woman who presented to the neurosurgery outpatient department with complaints of progressively increasing headache and diminished vision over the last year. On the clinical examination, the patient was conscious and oriented. The routine hematological and biochemical workup showed an increased erythrocyte sedimentation rate (ESR) and increased prolactin levels. The radiological working diagnosis was consistent with pituitary macroadenoma. No other radiological and/or clinical clue that could elicit the suspicion of pulmonary or extrapulmonary lesions of tuberculosis was found. The transsphenoidal endonasal tumor excision was done. The histopathology showed numerous epithelioid cell granulomas, Langhans giant cells along with scant necrosis. Ziehl Neelsen staining demonstrated acid-fast bacilli, and the final diagnosis of pituitary tuberculoma was made. We report this rare case of pituitary lesion that may be included in the differential diagnosis of sellar lesions to avoid unnecessary surgical interventions, especially in regions where the disease is endemic.

Cellular, Molecular, and Immunological Characteristics of Langhans Multinucleated Giant Cells Programmed by IL-15.

Langhans multinucleated giant cells (LGCs) are a specific type of multinucleated giant cell containing a characteristic horseshoe-shaped ring of nuclei that are present within granulomas of infectious etiology. Although cytokines that trigger macrophage activation (such as IFN-γ) induce LGC formation, it is not clear whether cytokines that trigger macrophage differentiation contribute to LGC formation. Here, we found that IL-15, a cytokine that induces M1 macrophage differentiation, programs human peripheral blood adherent cells to form LGCs. Analysis of the IL-15‒treated adherent cell transcriptome identified gene networks for T cells, DNA damage and replication, and IFN-inducible genes that correlated with IL-15 treatment and LGC-type multinucleated giant cell formation. Gene networks enriched for myeloid cells were anticorrelated with IL-15 treatment and LGC formation. Functional studies revealed that T cells were required for IL-15‒induced LGC formation, involving a direct contact with myeloid cells through CD40L-CD40 interaction and IFN-γ release. These data indicate that IL-15 induces LGC formation through the direct interaction of activated T cells and myeloid cells.

Cystic neutrophilic granulomatous mastitis: an update.

Cystic neutrophilic granulomatous mastitis (CNGM) is a rare subtype of granulomatous mastitis with a highly distinct histological pattern often associated with Corynebacterium species. CNGM is characterised by suppurative lipogranulomas that are composed of central lipid vacuoles rimmed by neutrophils and an outer cuff of epithelioid histiocytes. Some of the lipid vacuoles may contain sparse, rod-shaped, gram-positive bacilli that can be easily missed or dismissed. The surrounding mixed inflammatory infiltrate contains Langhans-type giant cells, lymphocytes and neutrophils. CNGM occurs in reproductive age women with a history of pregnancy and typically presents as a palpable mass that can be painful. CNGM has many mimickers, most significantly breast carcinoma. In many cases, CNGM has significant pathological and clinical overlap with other forms of granulomatous mastitis. Given the association with Corynebacterium species, early diagnosis of CNGM is essential in offering patients the most appropriate treatment. Prolonged antibiotic therapy specifically directed to corynebacteria is required, sometimes even beyond resolution of clinical symptoms. This comprehensive review of the existing literature on CNGM describes clinical-pathological features, microbiological findings, challenges associated with the microscopic differential diagnosis, clinical implications of this diagnosis and emerging treatment options. Morphological criteria and suggested comments to convey the degree of diagnostic certainty are also proposed for standard pathology reporting.

Interleukin-22 receptor 1 is expressed in multinucleated giant cells: A study on intestinal tuberculosis and Crohn's disease.

BACKGROUND: It is challenging to distinguish intestinal tuberculosis from Crohn's disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn's disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1ß rs1143627, TGFß rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study.

The protein alpha-synuclein (α-Syn) has been linked to neuroinflammatory conditions. We investigated whether the presence of α-Syn in peripheral tissues is a surrogate of brain inflammatory status in a small group of relapsing-remitting multiple sclerosis (RRMS) patients in a pilot cross-sectional study. Skin biopsies and peripheral blood were sampled from 34 healthy controls and 23 MS patients for measurement of α-Syn levels. Within the RRMS group 15 patients were in remission, and 8 patients were in the relapsing phase. The protein α-Syn was evaluated by means of immunohistochemistry and flow cytometry in skin and nucleated blood cells, respectively. In the skin, α-Syn levels were lower in relapsing MS than in the other groups, both in positive area (p = .021) and staining intensity (p = .004). In blood, the percentage of α-Syn-positive lymphocytes and monocytes were not statistically different between study groups. Moreover, the use of systemic steroids did not affect α-Syn positivity in MS-relapse patients. Finally, epidermic Langerhans cells did not stain positively for α-Syn. Overall, the levels of α-Syn positivity were lower in inflammatory relapse of RRMS patients when measured in peripheral tissues. We discuss the role of α-Syn levels in inflammation according to the obtained results.

Tuberculosis of the Cheek: A Rare Presentation.

Tuberculosis (TB) typically attacks the lungs. The oral lesions either primary or secondary are rarely seen and often overlooked by the clinician. More so, their atypical presentations make the diagnosis challenging; especially when they are present before the systemic symptoms become apparent. We report a case of primary tuberculosis in a 4 year old female child in a very uncommon location, the cheek. The timely diagnosis and antitubercular therapy resulted in complete resolution of the swelling within 6 months.

Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis.

BACKGROUND: Multinucleated giant cells have been noticed in diverse arthritic conditions since their first description in rheumatoid synovium. However, their role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA) still remains broadly unknown. We aimed to study the presence and characteristics of multinucleated giant cells (MGC) both in synovium and in subchondral bone tissues of patients with OA or RA. METHODS: Knee synovial and subchondral bone samples were from age-matched patients undergoing total joint replacement for OA or RA, or non-arthritic post mortem (PM) controls. OA synovium was stratified by histological inflammation grade using index tissue sections. Synovitis was assessed by Krenn score. Histological studies employed specific antibodies against macrophage markers or cathepsin K, or TRAP enzymatic assay. RESULTS: Inflamed OA and RA synovia displayed more multinucleated giant cells than did non-inflamed OA and PM synovia. There was a significant association between MGC numbers and synovitis severity. A TRAP negative/cathepsin K negative Langhans-like subtype was predominant in OA, whereas both Langhans-like and TRAP-positive/cathepsin K-negative foreign-body-like subtypes were most commonly detected in RA. Plasma-like and foam-like subtypes also were observed in OA and RA synovia, and the latter was found surrounding adipocytes. TRAP positive/cathepsin K positive osteoclasts were only identified adjacent to subchondral bone surfaces. TRAP positive osteoclasts were significantly increased in subchondral bone in OA and RA compared to PM controls. CONCLUSIONS: Multinucleated giant cells are associated with synovitis severity, and subchondral osteoclast numbers are increased in OA, as well as in RA. Further research targeting multinucleated giant cells is warranted to elucidate their contributions to the symptoms and joint damage associated with arthritis.

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

Abdominal tuberculosis: utility of laparoscopy in the correct diagnosis.

INTRODUCTION: Abdominal tuberculosis is one of the most prevalent form of extra-pulmonary disease, and the diagnosis is difficult because of non-specific clinical features. METHOD: We presented a case of a Tunisian woman with cough, nausea, decreased appetite and pelvic-abdominal pain. CT scan showed peritoneal thickening, peritoneal tiny nodules and enlarged mesenteric lymph nodes ascitic fluid. Sputum analysis was negative. Abdominal paracentesis was performed, and no malignant cell was detected. The Ziehl staining revealed a negativity for acid-fast bacilli. RESULTS: Diagnostic laparoscopy was performed. Biopsy specimens of peritoneum, liver, omentum and diaphragm showed omental epithelioid granulomas with a centrale caseous necrosis and Langhans giant cells. The patient received anti-tubercular treatment. CONCLUSIONS: In case of suspicion of tuberculosis, when bacteriologic and cytologic analysis is negative, laparoscopy with biopsies is helpful for correct diagnosis and appropriate management.

The T-SPOT.TB Test for Diagnosis of Breast Tuberculosis.

OBJECTIVE: To assess the diagnostic value of the T-SPOT.TB test in cases of breast turberculosis (BTB) in China. METHODS: We enrolled 13 female patients with primary BTB as the BTB test group and 10 healthy volunteers as the control group. The 2 groups underwent T-SPOT.TB tests and tuberculin skin tests (TSTs) before receiving a core-needle biopsy or excision biopsy. We then collected and analyzed T-SPOT.TB and TST data. RESULTS: The sensitivity of the T-SPOT.TB test for detection of BTB (84.6%) was significantly greater than that of TST (53.8%) (P <.05); the specificity of each test (80.0% and 60.0%, respectively) for BTB was not significantly different (P >.05). CONCLUSION: The T-SPOT.TB test could be a useful adjunct to current tests for diagnosis of BTB and could be used for early diagnosis of this condition.

Tumor-like Presentation of Tubercular Brain Abscess: Case Report

A 17-year-old girl presented with complaints of headache and decreasing vision of one month's duration, without any history of fever, weight loss, or any evidence of an immuno-compromised state. Her neurological examination was normal, except for papilledema. Laboratory investigations were within normal limits, except for a slightly increased Erythrocyte Sedimentation Rate (ESR). Non-contrast computerized tomography of her head revealed complex mass in left frontal lobe with a concentric, slightly hyperdense, thickened wall, and moderate perilesional edema with mass effect. Differential diagnoses considered in this case were pilocytic astrocytoma, metastasis and abscess. Magnetic resonance imaging (MRI) obtained in 3.0 Tesla (3.0T) scanner revealed a lobulated outline cystic mass in the left frontal lobe with two concentric layers of T2 hypointense wall, with T2 hyperintensity between the concentric ring. Moderate perilesional edema and mass effect were seen. Post gadolinium study showed a markedly enhancing irregular wall with some enhancing nodular solid component. No restricted diffusion was seen in this mass in diffusion weighted imaging (DWI). Magnetic resonance spectroscopy (MRS) showed increased lactate and lipid peaks in the central part of this mass, although some areas at the wall and perilesional T2 hyperintensity showed an increased choline peak without significant decrease in N-acetylaspartate (NAA) level. Arterial spin labelling (ASL) and dynamic susceptibility contrast (DSC) enhanced perfusion study showed decrease in relative cerebral blood volume at this region. These features in MRI were suggestive of brain abscess. The patient underwent craniotomy with excision of a grayish nodular lesion. Abundant acid fast bacilli (AFB) in acid fast staining, and epithelioid cell granulomas, caseation necrosis and Langhans giant cells in histopathology, were conclusive of tubercular abscess. Tubercular brain abscess is a rare manifestation that simulates malignancy and cause diagnostic dilemma. MRI along with MRS and magnetic resonance perfusion studies, are powerful tools to differentiate lesions in such equivocal cases.

Modulation of osteoclastogenesis with macrophage M1- and M2-inducing stimuli.

Macrophages are generated through the differentiation of monocytes in tissues and they have important functions in innate and adaptive immunity. In addition to their roles as phagocytes, macrophages can be further differentiated, in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), into osteoclasts (multinucleated giant cells that are responsible for bone resorption). In this work, we set out to characterize whether various inflammatory stimuli, known to induce macrophage polarization, can alter the type of multinucleated giant cell obtained from RANKL differentiation. Following a four-day differentiation protocol, along with lipopolysaccharide (LPS)/interferon gamma (IFNγ) as one stimulus, and interleukin-4 (IL-4) as the other, three types of multinucleated cells were generated. Using various microscopy techniques (bright field, epifluorescence and scanning electron), functional assays, and western blotting for osteoclast markers, we found that, as expected, RANKL treatment alone resulted in osteoclasts, whereas the addition of LPS/IFNγ to RANKL pre-treated macrophages generated Langhans-type giant cells, while IL-4 led to giant cells resembling foreign body giant cells with osteoclast-like characteristics. Finally, to gain insight into the modulation of osteoclastogenesis, we characterized the formation and morphology of RANKL and LPS/IFNγ-induced multinucleated giant cells.

Second-generation Langerhans cells originating from epidermal precursors are essential for CD8+ T cell priming.

In vivo studies questioned the ability of Langerhans cells (LCs) to mediate CD8(+) T cell priming. To address this issue, we used intradermal immunization with plasmid DNA, a system in which activation of CD8(+) T cells depends on delayed kinetics of Ag presentation. We found that dendritic cells (DCs) located in the skin at the time of immunization have limited ability to activate CD8(+) T cells. This activity was mediated by a second generation of DCs that differentiated in the skin several days after immunization, as well as by lymph node-resident DCs. Intriguingly, CD8(+) T cell responses were not affected following treatment with clodronate liposomes, immunization of CCR2(-/-) mice, or local neutralization of CCL20. This suggests that local, rather than blood-derived, DC precursors mediate CD8(+) T cell priming. Analysis of DC differentiation in the immunized skin revealed a gradual increase in the number of CD11c(+) cells, which reached their maximum 2 wk after immunization. A similar differentiation kinetics was observed for LCs, with the majority of differentiating LCs proliferating in situ from epidermal precursors. By using B6/Langerin-diphtheria toxin receptor chimeric mice and LC ablation, we demonstrated that epidermal LCs were crucial for the elicitation of CD8(+) T cell responses in vivo. Furthermore, LCs isolated from lymph nodes 2 wk after immunization contained the immunization plasmid and directly activated Ag-specific CD8(+) T cells ex vivo. Thus, these results indicate that second-generation Ag-expressing LCs differentiating from epidermal precursors directly prime CD8(+) T cells and are essential for optimal cellular immune responses following immunization with plasmid DNA.

Endometrial tuberculosis causing amenorrhea and abnormal uterine bleeding in a lupus patient treated with cyclophosphamide

BACKGROUND: Amenorrhea may occur in patients with lupus treated with cyclophosphamide. This is commonly attributed to primary ovarian failure leading to infertility -- a possible complication of cyclophosphamide. Urogenital tuberculosis (TB) can be a rare cause of amenorrhea and infertility in lupus patients.OBJECTIVE: To present a case of endometrial TB causing amenorrhea and abnormal uterine bleeding in a patient with lupus nephritis treated with cyclophosphamide.CASE: A 32-year-old Filipino female, who was diagnosed with lupus nephritis, was managed with high dose steroid and intravenous (IV) cyclophosphamide. Lupus nephritis improved with treatment, but she subsequently developed amenorrhea and vaginal spotting for two months. Symptoms were initially attributed to premature ovarian failure due to cyclophosphamide.Gynecologic examination showed thickened endometrium with normal ovaries and uterus on ultrasound. Dilatation and curettage was performed. Histopathology of endometrial curetting revealed chronic granulomatous endometritis with Langhans giant cells. Endometrial TB was diagnosed, and anti-Koch's therapy was started. The patient showed a favourable response, with resumption of normal menstruation after only the first month of treatment.CONCLUSION: This paper emphasizes the importance of considering a wide range of differential diagnosis for gynecologic symptoms in patients with lupus. Tuberculosis should be considered in areas of high endemicity

Tuberculosis of the entheses.

PURPOSE: Tuberculosis of the osteoarticular system usually manifests as joint arthritis. There is no available English literature on the tubercular involvement of the enthesis (tendon-bone junction). METHODS: We performed a retrospective analysis on 14 patients with tuberculosis of the tendon-bone junction. Patients presenting with a sinus with or without presence of radiological evidence of bone destruction around the enthesis, and pain unresponsive to a trial of analgesics and physical therapy, were evaluated by closed or open biopsy for tuberculosis. A staging system is proposed for biopsy-proven tuberculosis of the enthesis. RESULTS: Between 2006 and 2010, we treated 14 patients with tuberculosis of the tendon-bone junction. Biopsy-proven cases of tuberculosis of the enthesis were administered anti-tubercular drugs for a period of one year. Sequestrectomy was performed in advanced lesions. The tendon-bone junction was rested until the features of its healing were clinically evident. The patients aged between 18 and 52 years were followed up for an average of 1.7 years after cessation of anti-tubercular drug therapy. They responded favourably, and none had recurrence of the disease. CONCLUSIONS: This study describes the tubercular involvement of the entheses, which heretofore has not been described in the literature. The rarity of its occurrence and lack of suspicion of an infectious aetiology in these locations frequently results in late diagnosis and incorrect initial treatment. This study also supports the "microtrauma theory" in the genesis of osteoarticular tuberculosis.

Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant cells.

Cellular fusion of macrophages into multinucleated giant cells is a distinguishing feature of the granulomatous response to inflammation, infection, and foreign bodies (Kawai and Akira. 2011. Immunity 34: 637-650). We observed a marked increase in fusion of macrophages genetically deficient in Dicer, an enzyme required for canonical microRNA (miRNA) biogenesis. Gene expression profiling of miRNA-deficient macrophages revealed an upregulation of the IL-4-responsive fusion protein Tm7sf4, and analyses identified miR-7a-1 as a negative regulator of macrophage fusion, functioning by directly targeting Tm7sf4 mRNA. miR-7a-1 is itself an IL-4-responsive gene in macrophages, suggesting feedback control of cellular fusion. Collectively, these data indicate that miR-7a-1 functions to regulate IL-4-directed multinucleated giant cell formation.

The CD40-CD40L axis and IFN-γ play critical roles in Langhans giant cell formation.

The presence of Langhans giant cells (LGCs) is one of the signatures of systemic granulomatous disorders such as tuberculosis and sarcoidosis. However, the pathophysiological mechanism leading to LGC formation, especially the contribution of the T cells abundantly found in granulomas, has not been fully elucidated. To examine the role of T cells in LGC formation, a new in vitro method for the induction of LGCs was developed by co-culturing human monocytes with autologous T cells in the presence of concanavalin A (ConA). This system required close contact between monocytes and T cells, and CD4+ T cells were more potent than CD8+ T cells in inducing LGC formation. Antibody inhibition revealed that a CD40-CD40 ligand (CD40L) interaction and IFN-γ were essential for LGC formation, and the combination of exogenous soluble CD40L (sCD40L) and IFN-γ efficiently replaced the role of T cells. Dendritic cell-specific transmembrane protein (DC-STAMP), a known fusion-related molecule in monocytes, was up-regulated during LGC formation. Moreover, knock-down of DC-STAMP by siRNA inhibited LGC formation, revealing that DC-STAMP was directly involved in LGC formation. Taken together, these results demonstrate that T cells played a pivotal role in a new in vitro LGC formation system, in which DC-STAMP was involved, and occurred via a molecular mechanism that involved CD40-CD40L interaction and IFN-γ secretion.