CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection

Brian J. Laidlaw, Nianzhi Zhang, Heather D. Marshall, Mathew M. Staron, Tianxia Guan, Yinghong Hu, Linda S. Cauley, Joe Craft, Susan M. Kaech

Research output: Contribution to journalArticle

158 Scopus citations


Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4+ Tcells are important for the formation of functional lung-resident CD8+ Tcells after influenza virus infection. In the absence of CD4+ Tcells, CD8+ Tcells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8+ Tcells to the lung airways upon heterosubtypic challenge. CD4+ Tcell-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 areduction in T-bet rescued CD103 expression in the absence of CD4+ Tcell help. Thus, CD4+ Tcell-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.

Original languageEnglish
Pages (from-to)633-645
Number of pages13
Issue number4
StatePublished - Oct 16 2014

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