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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Immunologic Memory*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Integrin alpha Chains / immunology
  • Interferon-gamma / immunology
  • Lung / cytology
  • Lung / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Orthomyxoviridae Infections / immunology*
  • T-Box Domain Proteins / biosynthesis*


  • Antigens, CD
  • Integrin alpha Chains
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • alpha E integrins
  • Interferon-gamma