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Mucosal Immunol. 2019 Jul 5. doi: 10.1038/s41385-019-0183-z. [Epub ahead of print]

T-bet optimizes CD4 T-cell responses against influenza through CXCR3-dependent lung trafficking but not functional programming.

Author information

1
Burnett School of Biomedical Sciences, Division of Immunity and Pathogenesis, College of Medicine, University of Central Florida, Orlando, FL, USA.
2
NanoScience Technology Center, University of Central Florida, Orlando, FL, USA.
3
Wadsworth Center, Albany, NY, USA.
4
Burnett School of Biomedical Sciences, Division of Immunity and Pathogenesis, College of Medicine, University of Central Florida, Orlando, FL, USA. kai.mckinstry@ucf.edu.
5
NanoScience Technology Center, University of Central Florida, Orlando, FL, USA. kai.mckinstry@ucf.edu.

Abstract

Although clearance of many intracellular pathogens requires T-bet-dependent CD4 T cell programming, the extent to which T-bet is needed to direct protective CD4 responses against influenza is not known. Here, we characterize wild-type and T-bet-deficient CD4 cells during murine influenza infection. Surprisingly, although T-bet expression has broad impacts on cytokine production by virus-specific CD4 cells, the protective efficacy of T-bet-deficient effector cells is only marginally reduced. This reduction is due to lower CXCR3 expression, leading to suboptimal accumulation of activated T-bet-deficient cells in the infected lung. However, T-bet-deficient cells outcompete wild-type cells to form lung-resident and circulating memory populations following viral clearance, and primed T-bet-deficient mice efficiently clear supralethal heterosubtypic influenza challenges even when depleted of CD8 T cells. These results are relevant to the identification of more incisive correlates of protective T cells and for vaccines that aim to induce durable cellular immunity against influenza.

PMID:
31278374
DOI:
10.1038/s41385-019-0183-z

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