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

Summary 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.