Th1 may play an important role in SLE progression
In vivo inflammation is induced by the immune complex, and if
further activated, it can result in multiple organ injuries and promote
the development of disease in SLE 43. A previous study
reported that the levels of multiple cytokines in the serum were
increased in MRL/lpr mice 44, and researchers also
believe that the polarization of T cells in SLE involves changes from
Th1 to Th2 cells and that IFN-α promotes the differentiation of
activated B cells into plasma cells, thus playing an essential role in
the progression of disease 45, 46. Recently, detailed
research has begun to reveal the important role that IFN-γ plays in the
development of lupus in MRL/lpr mice 44, 47-49.
Firstly, serum IFN-γ levels have been found to be significantly higher
in both SLE patients and SLE murine models 44, 47.
IFN-γ has been demonstrated to dramatically promote the proliferation
and accumulation of DN T cells and to significantly increase the
expression of FasL on the surfaces of DN T cells in lupus mice48, 49. Simultaneously, the accumulation of plasma
cells is regarded to be a cardinal character in SLE 12,
21-23. Meanwhile, researchers have recently identified that the
majority of accumulated plasma cells are expressed in the T cell marker
CD3 and that the majority of these CD138+ T cells are also DN T cells12, 14. These findings suggest that these abnormal T
cells may play a more important role in SLE, but not only in B cells.
Previous studies have also shown that the frequency of Th1 cells in
Fas-deficient lupus mice are significantly higher in vivo , but
this is not true for Th2 12, 50. Evidence suggests
that IFN-γ-/- lpr mice exhibit significantly relieved symptoms of lupus,
compared with IFN-γ+/+ lpr mice 48. IFN-RII deficiency
has been suggested to significantly protect MRL/lpr mice from the
development of significant autoimmune associated lymphadenopathy,
autoantibodies, and renal disease, compared with IFN-RI deficiency in
MRL/lpr mice 51, 52. These results indicate that IFN-γ
and Th1 cells may be involved in the mechanisms of lupus development and
tissue injuries in MRL/lpr mice. Recent research has even proposed that
IFN-γ is required for the TLR7-promoted development of autoreactive B
cells 51.