Open AccessSkin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity
Author(s) -
Michael Hiltensperger,
Eduardo Beltrán,
Ravi Kant,
Sofia Tyystjärvi,
Gildas Lepennetier,
Helena Domínguez Moreno,
Isabel Bauer,
Simon Grassmann,
Sebastian Jarosch,
Kilian Schober,
Veit R. Buchholz,
Selin Kenet,
Christiane Gasperi,
Rupert Öllinger,
Roland Rad,
Andreas Muschaweckh,
Christopher Sie,
Lilian Aly,
Benjamin Knier,
Garima Garg,
Ali Maisam Afzali,
Lisa Ann Gerdes,
Tania Kümpfel,
Sören Franzenburg,
Naoto Kawakami,
Bernhard Hemmer,
Dirk H. Busch,
Thomas Misgeld,
Klaus Dornmair,
Thomas Korn
Publication year - 2021
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-021-00948-8
Subject(s) - priming (agriculture) , t helper cell , biology , t cell , immunology , autoimmunity , immune system , homing (biology) , cytotoxic t cell , antigen presenting cell , adoptive cell transfer , in vitro , genetics , ecology , botany , germination
Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6 + , and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.