A Context-Dependent Role for IL-21 in Modulating the Differentiation, Distribution, and Abundance of Effector and Memory CD8 T Cell Subsets

作者：Tian Yuan; Cox Maureen A; Kahan Shannon M; Ingram Jennifer T; Bakshi Rakesh K; Zajac Allan J^*

来源：The Journal of Immunology, 2016, 196(5): 2153-2166.

DOI：10.4049/jimmunol.1401236

The activation of naive CD8 T cells typically results in the formation of effector cells (T-E) 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 (T-EM), and tissue-resident memory (T-RM) 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 T-E/T-EM populations. The inability to perceive IL-21 signals under competitive conditions also resulted in lower levels of T-RM 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 alpha(4)beta(7) 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 T-E/T-EM and T-RM 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.

• 出版日期2016-3-1