Altered Expression Of Sirp Gamma On The T-Cells Of Relapsing Remitting Multiple Sclerosis And Type 1 Diabetes Patients Could Potentiate Effector Responses From T-Cells

Factors regulating self-antigen directed immune-responses in autoimmunity are poorly understood. Signal regulatory protein gamma (SIRP gamma) is a human T-cell specific protein with genetic variants associated with type 1 diabetes (T1D). SIRP gamma's function in the immune system remains unclear. We show that T1D and relapsing remitting multiple sclerosis (RRMS) subjects have significantly greater frequency of rs2281808 T genetic variant, that correlates with reduced SIRP gamma-expression in T-cells. Importantly, reduced SIRP gamma-expression in RRMS and T1D subjects was not restricted to T variant, suggesting SIRP gamma-expression is also regulated by disease specific factors in autoimmunity. Interestingly, increased frequencies of SIRP gamma T-low-cells in RRMS and T1D positively correlated with proinflammatory molecules from T-cells. Finally, we show that SIRP gamma T-low-cells have enhanced pathogenecityin vivoin a GVHD model. These findings suggest that decreased-SIRP gamma expression, either determined by genetic variants or through peripherally acquired processes, may have a mechanistic link to autoimmunity through induction of hyperactive T-cells.