A context-dependent role for IL-21 in modulating the differentiation, distribution, and abundance of effector and memory CD8 T cell subsets

• Published in: The Journal of immunology (1950) Vol. 196; no. 1_Supplement; pp. 133 - 133.17
• Main Authors: Tian, Yuan, Cox, Maureen A, Kahan, Shannon M, Ingram, Jennifer T, Bakshi, Rakesh K, Zajac, Allan J
• Format: Journal Article
• Language: English
• Published: 01.05.2016
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.133.17

Abstract The activation of naïve 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 (TCM), 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 the IL-21 receptor (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. Furthermore, IL-21 differentially promoted the expression of the chemokine receptor CX3CR1 and the integrin α4β7 on circulating CD8 T cells in the mixed bone marrow chimeras and on CD8 T cells primed in vitro. Thus, IL-21 may influence CD8 T cell migration by modulating the expression of CX3CR1 and α4β7. 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 tissues under lymphopenic conditions. 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.