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).