T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria

Th1 cells can be activated by tcr-independent stimuli,but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. here,we used a simple model of non-cognate th1 cell stimulation in salmonella-infected mice to examine these issues. cd4 th1 cell expression of both il-18r and dr3 was required for optimal ifn-γ induction in response to non-cognate stimulation,while il-15r expression was dispensable. interestingly,effector th1 cells generated by immunization rather than live infection had lower non-cognate activity despite comparable il-18r and dr3 expression. mice lacking t cell intrinsic expression of myd88,an important adapter molecule in non-cognate t cell stimulation,exhibited higher bacterial burdens upon infection with salmonella,chlamydia or brucella,suggesting that non-cognate th1 stimulation is a critical element of efficient bacterial clearance. thus,il-18r and dr3 are critical players in non-cognate stimulation of th1 cells and this response plays an important role in protection against intracellular bacteria. © 2017 pham et al.