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Regulation of CD 4 T cells and their effects on immunopathological inflammation following viral infection
Author(s) -
Bhattacharyya Mitra,
Madden Patrick,
Henning Nathan,
Gregory Shana,
Aid Malika,
Martinot Amanda J.,
Barouch Dan H.,
PenalozaMacMaster Pablo
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12771
Subject(s) - immunology , biology , immune system , adoptive cell transfer , inflammation , interferon , t cell , acquired immune system , interleukin 21 , cytotoxic t cell , context (archaeology) , in vitro , paleontology , biochemistry
Summary CD 4 T cells help immune responses, but knowledge of how memory CD 4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus‐specific CD 4 T cells, we show that naive CD 4 T cells undergo substantial expansion following infection, but can induce lethal T helper type 1‐driven inflammation. In contrast, memory CD 4 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 CD 4 T cells, but does not seem to play a critical role in regulating the expansion of secondary CD 4 T cells. Strikingly, blockade of type I interferon abrogated lethal inflammation by primary CD 4 T cells following viral infection, despite that this treatment increased the numbers of primary CD 4 T‐cell responses. Altogether, these data demonstrate important aspects of how primary and secondary CD 4 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.