Inflammatory monocytes contribute to the persistence of <scp>CXCR</scp>3^hi<scp>CX</scp>3<scp>CR</scp>1^lo circulating and lung‐resident memory <scp>CD</scp>8⁺ T cells following respiratory virus infection

<jats:title>Abstract</jats:title><jats:p>Phenotypically diverse memory <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> T cells are present in the lungs that either re‐circulate or reside within the tissue. Understanding the key cellular interactions that regulate the generation and then persistence of these different subsets is of great interest. Recently, <jats:styled-content style="fixed-case">DNGR</jats:styled-content>‐1<jats:sup>+</jats:sup> dendritic cell (<jats:styled-content style="fixed-case">DC</jats:styled-content>) mediated priming was reported to control the generation of lung‐resident but not circulating memory cells following respiratory viral infection. Here, we report an important role for Ly6C<jats:sup>+</jats:sup> inflammatory monocytes (<jats:styled-content style="fixed-case">IM</jats:styled-content>s) in contributing to the persistence of memory <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> T cells but not their generation. Effector <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> T cells expanded and contracted normally in the absence of <jats:styled-content style="fixed-case">IM</jats:styled-content>s, but the memory compartment declined significantly over time. Quite unexpectedly, this defect was confined to tissue resident and circulating <jats:styled-content style="fixed-case">CXCR</jats:styled-content>3<jats:sup>hi</jats:sup><jats:styled-content style="fixed-case">CX</jats:styled-content>3<jats:styled-content style="fixed-case">CR</jats:styled-content>1<jats:sup>lo</jats:sup> memory cells but not <jats:styled-content style="fixed-case">CXCR</jats:styled-content>3<jats:sup>hi</jats:sup><jats:styled-content style="fixed-case">CX</jats:styled-content>3<jats:styled-content style="fixed-case">CR</jats:styled-content>1<jats:sup>int</jats:sup> and <jats:styled-content style="fixed-case">CXCR</jats:styled-content>3<jats:sup>lo</jats:sup><jats:styled-content style="fixed-case">CX</jats:styled-content>3<jats:styled-content style="fixed-case">CR</jats:styled-content>1<jats:sup>hi</jats:sup> subsets. Thus, two developmentally distinct innate cells orchestrate the generation and persistence of memory T cell subsets following a respiratory virus infection.</jats:p><jats:p>See also: News and Commentary by <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://doi.org/10.1111/imcb.12036">Lafouresse & Groom</jats:ext-link></jats:p>