Skin-resident memory CD8 ⁺ T cells trigger a state of tissue-wide pathogen alert

<jats:title>Resident memory T cells sound the alarm</jats:title> <jats:p> Immunological memory protects against reinfection. Resident memory T cells (T <jats:sub>RM</jats:sub> ) are long-lived and remain in the tissues where they first encountered a pathogen (see the Perspective by Carbone and Gebhardt). Schenkel <jats:italic>et al.</jats:italic> and Ariotti <jats:italic>et al.</jats:italic> found that CD8 <jats:sup>+</jats:sup> T <jats:sub>RM</jats:sub> cells act like first responders in the female reproductive tissue or the skin of mice upon antigen reencounter. By secreting inflammatory proteins, T <jats:sub>RM</jats:sub> cells rapidly activated local immune cells to respond, so much so that they protected against infection with an unrelated pathogen. Iijima and Iwasaki found that CD4 <jats:sup>+</jats:sup> T <jats:sub>RM</jats:sub> cells protected mice against reinfection with intravaginal herpes simplex virus 2. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6205" page="98" related-article-type="in-this-issue" vol="346" xlink:href="10.1126/science.1254536">98</jats:related-article> , p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6205" page="101" related-article-type="in-this-issue" vol="346" xlink:href="10.1126/science.1254803">101</jats:related-article> , p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6205" page="93" related-article-type="in-this-issue" vol="346" xlink:href="10.1126/science.1257530">93</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6205" page="40" related-article-type="in-this-issue" vol="346" xlink:href="10.1126/science.1259925">40</jats:related-article> </jats:p>