Involvement of dendritic cells in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown aetiology. It has been suggested that T helper type 1 (Th1) polarisation is associated with the pathophysiology of sarcoidosis, but the mechanism of skewing towards Th1 has not been elucidated. Dendritic cells (DCs) are known to regulate immune responses. This study was performed to determine whether DCs are involved in the aetiology of sarcoidosis. METHODS: The numbers of peripheral blood DCs in 24 patients with sarcoidosis were analysed and biopsy specimens from four patients were stained immunohistochemically using monoclonal antibodies. RESULTS: The numbers of both myeloid and lymphoid DC subsets were significantly decreased in the blood and mature DCs were found in the granulomas of patients with sarcoidosis. A number of interferon-gamma (IFN-gamma) producing T cells were also detected in the sarcoid granuloma, as well as many interleukin (IL)-4 producing T cells. Double staining of the biopsy specimen using anti-fascin and anti-CD3 antibodies showed an anatomical interaction between DCs and T cells. CONCLUSIONS: These findings suggest that the blood DC subsets may migrate into the affected tissues, contributing to the formation of the granulomas in sarcoidosis. It is hypothesised that the migrating DCs may regulate the T cell response in sarcoidosis, at least in the granulomatous lesions.

CD3+CD4-CD8-TCR-alphabeta+ T-cell lymphoma with clinical features of primary effusion lymphoma: an autopsy case.

We report an unusual case of T-cell lymphoma presenting as ascites. A 72-year-old HIV-negative woman was admitted to our hospital for abdominal discomfort associated with increasing abdominal girth over the course of 1 month. Physical examination showed a tense and distended abdomen and edema of the lower extremities. There was no hepatosplenomegaly or lymphadenopathy. A computed tomographic scan of the abdomen and chest showed massive ascites and pleural effusions, but there was no evidence of tumor masses or lymph node enlargement. The cytospin prepared from the peritoneal fluid was hypercellular and composed of a population of monotonous, large cells containing fine chromatin. No herpesvirus-8 (HHV-8) DNA was detected by polymerase chain reaction in the cells. Immunohistochemistry showed the neoplastic cells to be CD3+, CD4, CD7+. CD8-, CD34-, CD56, and TCR-alphabeta+. Repeated cytogenetic studies showed common abnormalities of del(1) (p11p22), +i(7)(ql0), and t(11:14)(q23;q11). The morphologic and immunologic findings were suggestive of peripheral T-cell lymphoma (PTCL), unspecified. This case suggests that some PTCLs with clonal chromosomal aberrations can exhibit peculiar serosal spreading in the absence of HHV-8 infection.

T cell interactions in active rheumatoid arthritis: insights from the human autologous mixed lymphocyte reaction as a model of T cell activation cascade.

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Using monoclonal anti-Leu8 antibody to isolate subpopulations of human CD4+ and CD8+ T cells, we have investigated the role of these subpopulations in the T cell activation cascade during the course of AMLR. In normal subjects, CD4+Leu8+ cells are necessary for the initiation of the AMLR response, and sequentially lead to activation and proliferation of both CD4+Leu8- cells and CD8+Leu8+ cells. The activated CD8+Leu8+ cells, in turn, induce CD8+Leu8- cells to generate proliferation of the latter cells. Soluble mediators could be involved in the T cell activation cascade induced by the AMLR. Patients with active rheumatoid arthritis have a profound defect in the AMLR. Further analysis indicates that rheumatoid arthritis CD8+ T cells are markedly defective as responding cells in the AMLR. The impaired AMLR response by CD8+ cells cannot be reconstituted with AMLR-derived supernatants from normal T cells. The data suggest that the defective CD8+ T cell function may contribute to the pathogenesis of the disease.