In both human and animal models of type 1 diabetes, there is infiltration of T cells and antigen-presenting cells into the pancreatic islets. The resulting beta-cell destruction is felt to be T cell mediated. T cells from patients with autoimmune diabetes respond to multiple islet proteins, but it is unknown which cells, macrophages, dendritic cells, and/or B lymphocytes present antigen to autoreactive T cells. Rituximab, a monoclonal CD20 antibody that results in transient B-cell depletion, is efficacious in treating another T cell-mediated autoimmune disease, rheumatoid arthritis. A clinical trial using rituximab in type 1 diabetes is under way. In this study, we examined the effects of in vitro B-cell depletion on the T-cell proliferative response to islet proteins, tetanus toxoid, and the T-cell mitogen concanavalin A. Magnetic cell separation was used to deplete B cells in vitro and cellular immunoblotting was used to assess proliferative responses to islet proteins in peripheral blood mononuclear cells (PBMCs). PBMCs from diabetes patients positive for T-cell proliferative responses to islet proteins, diabetes patients negative for T-cell proliferative responses to islet proteins, and normal controls were evaluated before and after B-cell depletion. The change in the mean proliferative response to islet proteins for all subjects before B-cell depletion and after B-cell depletion was not statistically significant (p = .5858). Moreover, the mean proliferative responses to tetanus toxoid and concanavalin A before and after B-cell depletion were also not found to differ significantly (p = .5081, p = .9555 respectively). Thus, the depletion of B cells in vitro does not appear to significantly affect the T-cell proliferative responses to islet proteins, tetanus toxoid, or concanavalin A. These results indicate that it is unlikely that B cells are the primary antigen-presenting cells for autoreactive T cells in autoimmune diabetes. Our results may be of importance in interpreting the results of the current clinical trial evaluating the use of rituximab to treat type 1 diabetes.
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