Regulation of follicular helper CD4 T cell (Tfh) and Th1 differentiation in vivo

La Jolla Institute For Immunology, La Jolla CA

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Abstract

The vast majority of current human vaccines function by eliciting protective antibody responses. Neutralizing antibodies are an important component of protective immunity against a wide range of viral infections in humans and in animal models. T cell help to B cells is a fundamental aspect of adaptive immunity to viruses and the generation of immunological memory. Follicular helper CD4 T cells (Tfh) are the specialized providers of help to B cells. Tfh cells depend on expression of the transcription factor Bcl6. Tfh cells are important for the formation of germinal centers. Once germinal centers are formed, Tfh cells are needed to maintain them and to regulate germinal center B cell differentiation into plasma cells and memory B cells. There is compelling evidence that Tfh cells are limiting for the magnitude of germinal centers and hence limiting for the germinal center derived high affinity antibodies, memory B cells, and long-lived plasma cells that are the basis of long term humoral immunity. Therefore, there is substantial potential for an understanding of Tfh cells to facilitate better antiviral immune responses and vaccine-elicited humoral immunity. Despite these recent advances, our understanding of Tfh cells is still in the early stages, and the transcription factor (TF) pathways that control Tfh differentiation and define Tfli functions remain poorly understood. In Project 1, we will identify, characterize, stratify, and interconnect TFs that control Tfh differentiation and function to an acute viral infection, while also determining important TF regulators of Th1 differentiation.