title: A Context-Dependent Role for IL-21 in Modulating the Differentiation, Distribution, and Abundance of Effector and Memory CD8 T Cell Subsets.
abstract: The activation of naive CD8 T cells typically results in the formation of effector cells (TE) as well as phenotypically distinct memory cells that are retained over time. Memory CD8 T cells can be further subdivided into central memory, effector memory (TEM), and tissue-resident memory (TRM) subsets, which cooperate to confer immunological protection. Using mixed bone marrow chimeras and adoptive transfer studies in which CD8 T cells either do or do not express IL-21R, we discovered that under homeostatic or lymphopenic conditions IL-21 acts directly on CD8 T cells to favor the accumulation of TE/TEM populations. The inability to perceive IL-21 signals under competitive conditions also resulted in lower levels of TRM phenotype cells and reduced expression of granzyme B in the small intestine. IL-21 differentially promoted the expression of the chemokine receptor CX3CR1 and the integrin α4β7 on CD8 T cells primed in vitro and on circulating CD8 T cells in the mixed bone marrow chimeras. The requirement for IL-21 to establish CD8 TE/TEM and TRM subsets was overcome by acute lymphocytic choriomeningitis virus infection; nevertheless, memory virus-specific CD8 T cells remained dependent on IL-21 for optimal accumulation in lymphopenic environments. Overall, this study reveals a context-dependent role for IL-21 in sustaining effector phenotype CD8 T cells and influencing their migratory properties, accumulation, and functions.
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Cox
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Kahan
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Ingram
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294.
authors.forename: Rakesh K
authors.identifier: http://orcid.org/0000-0003-2120-6625
authors.initials: RK
authors.lastname: Bakshi
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294 azajac@uab.edu.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D000098546:Interleukin-21
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