Intestinal tissue-resident memory T cells maintain distinct identity from circulating memory T cells after in vitro restimulation.

Autor: Beumer-Chuwonpad A; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, the Netherlands., Behr FM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, the Netherlands., van Alphen FPJ; Department of Research Facilities, Sanquin Research and Laboratory Services, Amsterdam, the Netherlands., Kragten NAM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, the Netherlands., Hoogendijk AJ; Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands., van den Biggelaar M; Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands., van Gisbergen KPJM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, the Netherlands.; Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 May; Vol. 54 (5), pp. e2350873. Date of Electronic Publication: 2024 Mar 19.
DOI: 10.1002/eji.202350873
Abstrakt: Resident memory T (T RM ) cells have been recently established as an important subset of memory T cells that provide early and essential protection against reinfection in the absence of circulating memory T cells. Recent findings showing that T RM expand in vivo after repeated antigenic stimulation indicate that these memory T cells are not terminally differentiated. This suggests an opportunity for in vitro T RM expansion to apply in an immunotherapy setting. However, it has also been shown that T RM may not maintain their identity and form circulating memory T cells after in vivo restimulation. Therefore, we set out to determine how T RM respond to antigenic activation in culture. Using Listeria monocytogenes and LCMV infection models, we found that T RM from the intraepithelial compartment of the small intestine expand in vitro after antigenic stimulation and subsequent resting in homeostatic cytokines. A large fraction of the expanded T RM retained their phenotype, including the expression of key T RM markers CD69 and CD103 (ITGAE). The optimal culture of T RM required low O 2 pressure to maintain the expression of these and other T RM -associated molecules. Expanded T RM retained their effector capacity to produce cytokines after restimulation, but did not acquire a highly glycolytic profile indicative of effector T cells. The proteomic analysis confirmed T RM profile retention, including expression of T RM -related transcription factors, tissue retention factors, adhesion molecules, and enzymes involved in fatty acid metabolism. Collectively, our data indicate that limiting oxygen conditions supports in vitro expansion of T RM cells that maintain their T RM phenotype, at least in part, suggesting an opportunity for therapeutic strategies that require in vitro expansion of T RM .
(© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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