Abstract
IL-15 induces the proliferation of memory CD8+ T cells. The expression of CD5 inversely correlates with the IL-15 responsiveness of human memory CD8+ T cells. However, whether CD5 directly regulates IL-15-induced proliferation is unknown. Here, we demonstrate that human memory CD8+ T cells in advanced differentiation stages respond to IL-15 better than those in less differentiated stages. Moreover, the expression level of CD5 was found as the best correlate for IL-15 hypo-responsiveness among human memory CD8+ T cells. Importantly, IL-15-induced proliferation is significantly enhanced by blocking CD5 with antibodies or knocking down CD5 expression using siRNA, indicating that CD5 directly suppresses the IL-15-induced proliferation of human memory CD8+ T cells. We also found that CD5 inhibits activation of the mTOR pathway, which is required for IL-15-induced proliferation. Taken together, the results indicate that CD5 is not just a correlative marker for IL-15 hypo-responsiveness, but also directly suppresses IL-15-induced proliferation of human memory CD8+ T cells by inhibiting mTOR pathways.
Published Version
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