Memory CD4 + T cells protect against influenza through multiple synergizing mechanisms

K. Kai McKinstry, Tara M. Strutt, Yi Kuang, Deborah M. Brown, Stewert Sell, Richard W. Dutton, Susan L. Swain

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Memory CD4 + T cells combat viral infection and contribute to protective immune responses through multiple mechanisms, but how these pathways interact is unclear. We found that several pathways involving memory CD4 + T cells act together to effectively clear influenza A virus (IAV) in otherwise unprimed mice. Memory CD4 + T cell protection was enhanced through synergy with naive B cells or CD8 + T cells and maximized when both were present. However, memory CD4 + T cells protected against lower viral doses independently of other lymphocytes through production of IFN-γ. Moreover, memory CD4 + T cells selected for epitope-specific viral escape mutants via a perforin-dependent pathway. By deconstructing protective immunity mediated by memory CD4 + T cells, we demonstrated that this population simultaneously acts through multiple pathways to provide a high level of protection that ensures eradication of rapidly mutating pathogens such as IAV. This redundancy indicates the need for reductionist approaches for delineating the individual mechanisms of protection mediated by memory CD4 + T cells responding to pathogens.

Original languageEnglish (US)
Pages (from-to)2847-2856
Number of pages10
JournalJournal of Clinical Investigation
Volume122
Issue number8
DOIs
StatePublished - Aug 1 2012

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Human Influenza
T-Lymphocytes
Influenza A virus
Perforin
T-Lymphocyte Epitopes
Cytoprotection
Virus Diseases
Immunity
B-Lymphocytes
Lymphocytes
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

McKinstry, K. K., Strutt, T. M., Kuang, Y., Brown, D. M., Sell, S., Dutton, R. W., & Swain, S. L. (2012). Memory CD4 + T cells protect against influenza through multiple synergizing mechanisms. Journal of Clinical Investigation, 122(8), 2847-2856. https://doi.org/10.1172/JCI63689

Memory CD4 + T cells protect against influenza through multiple synergizing mechanisms. / McKinstry, K. Kai; Strutt, Tara M.; Kuang, Yi; Brown, Deborah M.; Sell, Stewert; Dutton, Richard W.; Swain, Susan L.

In: Journal of Clinical Investigation, Vol. 122, No. 8, 01.08.2012, p. 2847-2856.

Research output: Contribution to journalArticle

McKinstry, KK, Strutt, TM, Kuang, Y, Brown, DM, Sell, S, Dutton, RW & Swain, SL 2012, 'Memory CD4 + T cells protect against influenza through multiple synergizing mechanisms', Journal of Clinical Investigation, vol. 122, no. 8, pp. 2847-2856. https://doi.org/10.1172/JCI63689
McKinstry, K. Kai ; Strutt, Tara M. ; Kuang, Yi ; Brown, Deborah M. ; Sell, Stewert ; Dutton, Richard W. ; Swain, Susan L. / Memory CD4 + T cells protect against influenza through multiple synergizing mechanisms. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 8. pp. 2847-2856.
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