A ROLE FOR NON-COGNATE CD4 T CELL ACTIVATION IN BACTERIAL CLEARANCE

CD4 Th1 cells are required for protective immunity to a variety of microbial pathogens but the relative contribution of cognate and non-cognate CD4 T cell activation is poorly understood. We previously demonstrated that Salmonella-specific CD4 T cells can be activated to produce IFN-g in a Myd88-dependent manner by a variety of innate stimuli. Here, we used mice with Myd88 deficiency in CD4 T cells to examine the contribution of non-cognate stimulation in protection against a variety of different infections. While bacterial clearance was significantly delayed following Salmonella or Chlamydia infection, CD4-myd88-deficient mice displayed normal clearance of Brucella and Plasmodium. Delayed clearance of Salmonella and Chlamydia correlated with a marked reduction in IFN-g production by CD4 Th1 cells in response to innate stimuli. This deficiency was specific in infection models since Th1 cells hat were generated by sub-unit vaccination were able to produce IFN-g normally. Together, these data support a model where non-cognate CD4 T cell activation develops in response to bacterial replication and makes a significant contribution to bacterial clearance.