The tyrosine kinase Itk suppresses CD8+ memory T cell development in response to bacterial infection

Vaccine efficacy depends on strong long-term development of immune memory and the formation of memory CD8(+) T cells is critical for recall responses to infection. Upon antigen recognition by naive T cells, the strength of the TcR signal influences the subsequent effector and memory cells differentiation. Here, we have examined the role of Itk, a tyrosine kinase critical for TcR signaling, in CD8(+) effector and memory T cell differentiation during Listeria monocytogenes infection. We found that the reduced TcR signal strength in Itk deficient naive CD8(+) T cells enhances the generation of memory T cells during infection. This is accompanied by increased early Eomesodermin, IL-7R alpha expression and memory precursor effector cells. Furthermore, Itk is required for optimal cytokine production in responding primary effector cells, but not secondary memory responses. Our data suggests that Itk-mediated signals control the expression of Eomesodermin and IL-7R alpha, thus regulating the development of memory CD8(+) T cells, but not subsequent response of memory cells.