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Competition within the virus‐specific CD4 T‐cell pool limits the T follicular helper response after influenza infection
Author(s) -
Olson Matthew R,
Chua Brendon Y,
GoodJacobson Kim L,
Doherty Peter C,
Jackson David C,
Turner Stephen J
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2016.42
Subject(s) - germinal center , biology , immunology , t cell , influenza a virus , adoptive cell transfer , b cell , virus , immune system , virology , antibody
CD4 T follicular helper cells (TFH) are critical in the generation of potent and long‐lived B‐cell responses after viral infection. However, the factors that dictate the generation and maintenance of these cells are not fully understood. Here we use adoptive transfer of OTII T‐cell receptor transgenic CD4 T cells, followed by infection with recombinant influenza A virus (IAV), as a means of identifying and tracking virus‐specific CD4 + T‐cell responses. We show that T‐cell competition within the virus‐specific CD4 T‐cell pool induced by IAV infection limits the proliferation and differentiation of IAV‐specific CD4 + TFH responses. In particular, increased T‐cell competition for antigen results in a diminished IAV‐specific TFH CD4 T‐cell responses, particularly germinal center TFH responses. Strikingly, competition in the form of preexisting cellular immunity generated by heterosubtypic IAV immunization limits de novo CD4 T‐cell responses in secondary lymphoid tissue. Taken together, these data show a profound linkage between antigen availability and promotion of TFH CD4 + T‐cell responses in response to infection. These data suggest that competition within the CD4 T‐cell pool limits TFH responses and may be an important regulatory mechanism for controlling immunity.