Possible Plasticity of Cytotoxic Resident Memory T Cells in Fixed Drug Eruption.

In addition to the sessile phenotype and prompt effector function of skin resident memory T (TRM) cells, which rise from circulating memory T cells, including central memory T (TCM) cells and effector memory T (TEM) cells ( Buggert et al., 2020 Buggert M. Vella L.A. Nguyen S. Wu V.H. Chen Z. Sekine T. et al. The identity of human tissue-emigrant CD8+ T cells. Cell. 2020; 183: 1946-1961.e15 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar ; Gehad et al., 2018 Gehad A. Teague J.E. Matos T.R. Huang V. Yang C. Watanabe R. et al. A primary role for human central memory cells in tissue immunosurveillance. Blood Adv. 2018; 2: 292-298 Crossref PubMed Scopus (23) Google Scholar ; Thome et al., 2014 Thome J.J. Yudanin N. Ohmura Y. Kubota M. Grinshpun B. Sathaliyawala T. et al. Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell. 2014; 159: 814-828 Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar ; Watanabe et al., 2015 Watanabe R. Gehad A. Yang C. Scott L.L. Teague J.E. Schlapbach C. et al. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci Transl Med. 2015; 7 (279ra39) Crossref Scopus (384) Google Scholar ), recent studies in murine models showed the plasticity of TRM cells, providing the systemic protection by bearing circulating populations upon antigen re-exposure ( Behr et al., 2020 Behr F.M. Parga-Vidal L. Kragten N.A.M. van Dam T.J.P. Wesselink T.H. Sheridan B.S. et al. Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses. Nat Immunol. 2020; 21: 1070-1081 Crossref PubMed Scopus (92) Google Scholar ; Fonseca et al., 2020 Fonseca R. Beura L.K. Quarnstrom C.F. Ghoneim H.E. Fan Y. Zebley C.C. et al. Developmental plasticity allows outside-in immune responses by resident memory T cells. Nat Immunol. 2020; 21: 412-421 Crossref PubMed Scopus (161) Google Scholar ). Still, it is difficult to directly adapt these findings in murine models to human biology ( Masopust et al., 2017 Masopust D. Sivula C.P. Jameson S.C. Of mice, dirty mice, and men: using mice to understand human immunology. J Immunol. 2017; 199: 383-388 Crossref PubMed Scopus (166) Google Scholar ). In human graft-versus-host disease, host-derived circulating ex-TRM cells contribute to systemic inflammation ( Strobl et al., 2021 Strobl J. Gail L.M. Kleissl L. Pandey R.V. Smejkal V. Huber J. et al. Human resident memory T cells exit the skin and mediate systemic Th2-driven inflammation. J Exp Med. 2021; 218e20210417 Crossref PubMed Scopus (23) Google Scholar ). However, the phenotypical changes of TRM cells have not been appreciated.