Specific help for T_RM cells

CD4⁺ T cells are important for the formation of memory CD8⁺ T cell responses through the licensing of dendritic cells and the generation of chemokine gradients in the draining lymph nodes. In Immunity, Kaech and colleagues show that CD4⁺ T cells also promote the formation of CD8⁺ tissue-resident T cells (T_RM cells) during infection of mice with influenza virus by promoting expression of the integrin CD103 on virus-specific CD8⁺ T_RM cells and, thus, their localization in the lung airway. In the absence of CD4⁺ T cell help to CD8⁺ T_RM cells, there is less recruitment of virus-specific CD8⁺ T cells and less protection during secondary infection. CD4⁺ T cell help is required during the first week of infection and is dependent on the production of interferon-γ by CD4⁺ T cells. CD8⁺ T_RM cells that did not receive help have higher expression of T-bet than their counterparts that did receive help, and high expression of this transcription factor represses the TGF-β-mediated induction of CD103 in virus-specific CD8⁺ T cells, which provides a potential mechanism for these observations.

Immunity 41, 633–645 (2014)