Activated CD4 T cells have the remarkable ability to differentiate into many different types of effector subsets. This diversification is required for the generation of specialized and pathogen appropriate T cell responses, as well as long-lived and protective memory T cells. Although CD4 memory T cells are clearly important to control various infections (i.e. tuberculosis), vaccines targeting the induction of polyfunctional memory cells have had only limited success. In some cases, CD4 memory T cells can also induce host detrimental effects, for example during chronic viral infection or after organ transplantation. We hypothesize that these divergent effects are dependent on heterogeneity within the CD4 memory T cell compartment, the plasticity of these cells following recall, and their localization relative to other cells or environmental signals. Thus, a major goal of our work is to elucidate the specific factors regulating CD4 memory T cell diversification and their relationship to host immunity. We are using several infection models as well as complementary microscopy approaches to assess the dynamics and flexibility of T cell differentiation.
