Enhancement of CD8T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8T cells in SLE.

Methods: Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor.

Results: Our results demonstrated that there was increased surface expression of CD107a of CD8T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner.

Conclusion: In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.