Competition within the virus-specific CD4 T-cell pool limits the T follicular helper response after influenza infection

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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 limitsde novoCD4 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.

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