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Immunity. 2014 Oct 16;41(4):633-45. doi: 10.1016/j.immuni.2014.09.007. Epub 2014 Oct 9.

CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection.

Author information

  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 2Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
  • 3Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
  • 4Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: joseph.craft@yale.edu.
  • 5Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA. Electronic address: susan.kaech@yale.edu.

Abstract

Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4(+) T cells are important for the formation of functional lung-resident CD8(+) T cells after influenza virus infection. In the absence of CD4(+) T cells, CD8(+) T cells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8(+) T cells to the lung airways upon heterosubtypic challenge. CD4(+) T cell-derived interferon-γ was necessary for generating lung-resident CD103(+) CD8(+) Trm cells. Furthermore, expression of the transcription factor T-bet was increased in "unhelped" lung Trm cells, and a reduction in T-bet rescued CD103 expression in the absence of CD4(+) T cell help. Thus, CD4(+) T cell-dependent signals are important to limit expression of T-bet and allow for the development of CD103(+) CD8(+) Trm cells in the lung airways following respiratory infection.

PMID:
25308332
[PubMed - indexed for MEDLINE]
PMCID:
PMC4324721
Free PMC Article
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