Circulating memory CD8 + T cells are limited in forming CD103 + tissue-resident memory T cells at mucosal sites after reinfection.

Autor: Behr FM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Beumer-Chuwonpad A; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Kragten NAM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Wesselink TH; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Stark R; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; BIH Center for Regenerative Therapies, Charité Universitätsmedizin Berlin, Berlin, Germany., van Gisbergen KPJM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2021 Jan; Vol. 51 (1), pp. 151-166. Date of Electronic Publication: 2020 Aug 31.
DOI: 10.1002/eji.202048737
Abstrakt: Tissue-resident memory CD8 + T cells (T RM ) localize to barrier tissues and mediate local protection against reinvading pathogens. Circulating central memory (T CM ) and effector memory CD8 + T cells (T EM ) also contribute to tissue recall responses, but their potential to form mucosal T RM remains unclear. Here, we employed adoptive transfer and lymphocytic choriomeningitis virus reinfection models to specifically assess secondary responses of T CM and T EM at mucosal sites. Donor T CM and T EM exhibited robust systemic recall responses, but only limited accumulation in the small intestine, consistent with reduced expression of tissue-homing and -retention molecules. Murine and human circulating memory T cells also exhibited limited CD103 upregulation following TGF-β stimulation. Upon pathogen clearance, T CM and T EM readily gave rise to secondary T EM . T CM also formed secondary central memory in lymphoid tissues and T RM in internal tissues, for example, the liver. Both T CM and T EM failed to substantially contribute to resident mucosal memory in the small intestine, while activated intestinal T RM , but not liver T RM , efficiently reformed CD103 + T RM . Our findings demonstrate that circulating T CM and T EM are limited in generating mucosal T RM upon reinfection. This may pose important implications on cell therapy and vaccination strategies employing memory CD8 + T cells for protection at mucosal sites.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: