CD138+ T cells may be autoreactive T cells that promote autoantibody production in a CD4 receptor-dependent manner
Previous research has demonstrated that DN T cells play an important role in the progression of disease and that they contribute to the tissue injury of SLE 6, 19, 20. The accumulation of plasma cells is also a cardinal feature of SLE 12, 21-23. Interestingly, meanwhile, the majority of CD138+ plasma cells in an SLE murine model have been revealed to be subsets of CD3+ and CD138+ T cells 12-14. Moreover, most CD138+ T cells are also DN T cells that are CD4 and CD8 double negative 12-14. Immature T cells experience positive selection and negative selection, thus becoming mature single positive T cells that cannot recognize self-antigens 24, 25. Auto-reactive T cells are deleted by Fas-mediated apoptosis during negative selection in the thymus 26. Fas-deficiency may allow auto-reactive T cells to pass through negative selection 27, 28. The production of autoantibodies has detrimental effects on multiple organs and plays a key role in the progression of diseases, such as SLE29. It was previously thought that SLE was mainly associated with autoreactive B cells 3-5 and was induced by the secretion of autoantibodies from plasma cells originating from autoreactive B cells 16. However, recent studies suggested that T cells may play a more important role in the development of SLE 6-8, 14. Importantly, recent research has demonstrated that CD138+ T cells significantly promote autoantibody production both in vivo and in vitro 7, 14, 30. It has also been suggested that CD138+ T cells may be key to uncovering the underlying mechanism of SLE.
It has been demonstrated that autoantibody production in lupus mice is dependent on CD4 expression, but not on the accumulation of DN T cells7, 14, 30. Simultaneously, CD138+ T cells have been shown to significantly increase autoantibody production in an SLE murine model, in a CD4 receptor dependent way. They have also been revealed to promote tissue injuries when self-antigens are exposed to the immune system 7, 14, 30. However, CD138+ T cells have been revealed to accumulate only in Fas-deficient lupus mice (i.e., not in non-lupus prone mice) 12-14. This finding indicates that Fas deficiency also results in the accumulation of CD138+ T cells in MRL/lpr mice, in addition to DN T cells. These results indicate that the accumulated CD138+ T cells are auto-reactive T cells that avoid apoptosis during negative selection (induced by Fas-dependent apoptosis)12-14. We speculate that the expression of CD138 in CD3+ T cells is therefore probably caused by the failure of activation in auto-reactive T cells before exposure to self-antigens. This likely induces the defective apoptosis of CD138+ T cells and the subsequent accumulation of CD138+ T cells in MRL/lpr mice. When auto-reactive B cells are activated by self-antigens, the auto-reactive CD4+ T cells may then be activated by the expression of major histocompatibility complex (MHC)-II in auto-reactive B cells. CD4+CD138+ T cells may therefore be the accumulated auto-reactive CD4+ T cells that activate auto-reactive B cells; they may promote the formation of the abnormal plasma cells that secrete autoantibodies (Figure 1).