Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection

5 years ago

Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection

Patrick Madden, Nathan Henning, Amanda J. Martinot, Malika Aid, Pablo Penaloza-MacMaster, Dan H. Barouch, Shana Gregory, Mitra Bhattacharyya

CD4 T cells help immune responses, but knowledge of how memory CD4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naive CD4 T cells undergo substantial expansion following infection, but can induce lethal T helper type 1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper cell subsets and were able to improve adaptive immune responses in the context of minimal tissue damage. Our analyses revealed that type I interferon regulates the expansion of primary CD4 T cells, but does not seem to play a critical role in regulating the expansion of secondary CD4 T cells. Strikingly, blockade of type I interferon abrogated lethal inflammation by primary CD4 T cells following viral infection, despite that this treatment increased the numbers of primary CD4 T-cell responses. Altogether, these data demonstrate important aspects of how primary and secondary CD4 T cells are regulated in vivo, and how they contribute to immune protection and immunopathology. These findings are important for rational vaccine design and for improving adoptive T-cell therapies against persistent antigens. Penaloza-MacMaster and colleagues show that memory CD4 T cells exhibit limited recall expansion, but are able to help adaptive immune responses in the context of minimal immunopathology.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/imm.12771