Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD4(+) T helper cells play a pivotal role in the pathogenesis of SLE, although the mechanism is still unclear. The present study was designed to isolate and characterize autoreactive T lymphocytes from BXSB mice, a mouse model for human SLE. Splenocytes from 6-month-old male BXSB mice with murine lupus were repeatedly stimulated in vitro with irradiated syngeneic B cells in the presence of recombinant IL-2, resulting in six autoreactive T-cell lines and two T-cell clones. TCR analysis showed that, one of the T-cell lines, ATL1, was almost clonal, as a Vbeta2.1-Jbeta2, a Valpha5.1-Jalpha15 and a Valpha10.1-Jalpha15 chains were predominantly expressed in this line. The two clones derived from ATL1 turned out to be sister clones, using the TCR Vbeta2.1-Jbeta2 and Valpha10.1-Jalpha15 chains. ATL1 cells proliferated in response to stimulation of syngeneic and H-2-matched allogeneic B cells and secreted IFN-gamma. Monoclonal Ab against CD4 and CD28 inhibited the proliferative response of ATL1 for syngeneic B cells. Interestingly, ATL1 did not respond to BXSB spleen or peritoneal macrophages, suggesting that B cells were able to either express accessory molecules necessary for T-cell triggering or present cryptic epitopes recognized by the autoreactive T cells. Moreover, ATL1 was able to help BXSB, but not C57BL/6, B cells producing IgG and IgM Abs against dsDNA and histone in vitro. Passive transfer of viable ATL1 cells into young female BXSB mice significantly accelerated the production of autoantibodies. Possible mechanisms of interaction between ATL1 and lupus B cells are further discussed.
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PMID:Isolation and functional analysis of autoreactive T cells from BXSB mice with murine lupus. 1236 58

Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactive T cell (ATL1) clone obtained from lupus-prone BXSB mice. ATL1 cells, either before or after gamma-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) were much more powerful stimulators for ATL1 cells on a per cell basis. The T cell stimulating ability of macrophages and B cells, but not DCs, was sensitive to gamma-ray irradiation. Monoclonal antibodies against mouse MHC-II and CD4 were able to block DC-mediated stimulation of ATL1 proliferation, indicating cognate recognition between ATL1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.
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PMID:Interaction between antigen presenting cells and autoreactive T cells derived from BXSB mice with murine lupus. 1729 82