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

Matthew R Olson, Brendon Y Chua, Kim L Good-Jacobson, Peter C Doherty, David C Jackson, Stephen J Turner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)729–740
Number of pages12
JournalImmunology and Cell Biology
Volume94
DOIs
Publication statusPublished - 19 Jul 2016

Cite this

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title = "Competition within the virus-specific CD4 T-cell pool limits the T follicular helper response after influenza infection",
abstract = "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.",
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Competition within the virus-specific CD4 T-cell pool limits the T follicular helper response after influenza infection. / Olson, Matthew R; Chua, Brendon Y; Good-Jacobson, Kim L; Doherty, Peter C; Jackson, David C; Turner, Stephen J.

In: Immunology and Cell Biology, Vol. 94, 19.07.2016, p. 729–740.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Olson, Matthew R

AU - Chua, Brendon Y

AU - Good-Jacobson, Kim L

AU - Doherty, Peter C

AU - Jackson, David C

AU - Turner, Stephen J

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AB - 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.

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