Chlamydia infections are a cause of blindness worldwide and a major cause of sexually transmitted disease in the US. Greater understanding of protective immunity to Chlamydia at mucosal surfaces is urgently required if an effective vaccine is to become a reality. This application will examine fundemental aspects of protective CD4 T cells during infection of the female reproductive tract mucosa. Our experimental approach is unique in that it utilizes a natural route of infection, uses an established model where CD4 T cells participate in bacterial clearance, and allows for direct visualization of endogenous and transferred Chlamydia-specific CD4 T cells. Our application specifically proposes to establish new mouse models to understand the mechanism of protection mediated by circulating memory CD4 T cells and, (i) determine whether innate lymphoid cells recruit memory cells to the FRT, (ii) examine the contribution of memory Th17 cells in coordinating bacterial clearance. Developing these infection models and addressing these issues will expand our knowledge of memory responses to Chlamydia and could be vitally important for the generation of a new vaccine for an important human pathogen.