CD8 + T cell self-tolerance permits responsiveness but limits tissue damage.

Autor:	Truckenbrod EN; Center for Immunology, University of Minnesota, Saint Paul, United States., Burrack KS; Center for Immunology, University of Minnesota, Saint Paul, United States., Knutson TP; Minnesota Supercomputing Institute, University of Minnesota, Saint Paul, United States., Borges da Silva H; Center for Immunology, University of Minnesota, Saint Paul, United States., Block KE; Center for Immunology, University of Minnesota, Saint Paul, United States., O'Flanagan SD; Center for Immunology, University of Minnesota, Saint Paul, United States., Stagliano KR; Center for Immunology, University of Minnesota, Saint Paul, United States., Hurwitz AA; Center for Immunology, University of Minnesota, Saint Paul, United States., Fulton RB; Center for Immunology, University of Minnesota, Saint Paul, United States., Renkema KR; Center for Immunology, University of Minnesota, Saint Paul, United States., Jameson SC; Center for Immunology, University of Minnesota, Saint Paul, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Apr 30; Vol. 10. Date of Electronic Publication: 2021 Apr 30.
DOI:	10.7554/eLife.65615
Abstrakt:	Self-specific CD8 + T cells can escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8 + T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice expressing or lacking this enzyme (due to deficiency in Dct , which encodes Trp2). Phenotypic and gene expression profiles of pre-immune Trp2/K b -specific cells were similar; the size of this population was only slightly reduced in wild-type (WT) compared to Dct -deficient ( Dct -/- ) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/K b -specific cells showed blunted expansion and less readily differentiated into a CD25 + proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/K b -specific cells mediated vitiligo much less efficiently. Hence, CD8 + T cell self-specificity is poorly predicted by precursor frequency, phenotype, or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells. Competing Interests: ET, KB, TK, HB, KB, SO, KS, KR, SJ No competing interests declared, AH is affiliated with AgenTus Therapeutics, Inc. The author has no financial interests to declare. RF is affiliated with HiFiBio, Inc. The author has no financial interests to declare.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu