Antigen-Independent Differentiation and Maintenance of Effector-like Resident Memory T Cells in Tissues

被引:504
作者
Casey, Kerry A. [1 ]
Fraser, Kathryn A. [1 ]
Schenkel, Jason M. [1 ]
Moran, Amy
Abt, Michael C. [2 ,3 ,4 ]
Beura, Lalit K. [1 ]
Lucas, Philip J. [5 ]
Artis, David [2 ,3 ]
Wherry, E. John [2 ,3 ]
Hogquist, Kristin
Vezys, Vaiva [1 ]
Masopust, David [1 ]
机构
[1] Univ Minnesota, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USA
[2] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA
[3] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA
[5] NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
INTRAEPITHELIAL LYMPHOCYTES; PROMOTES DIFFERENTIATION; INTESTINAL EPITHELIUM; NONLYMPHOID TISSUE; VIRAL-INFECTION; FACTOR-BETA; IN-VIVO; RECEPTOR; SUBSETS; EXPRESSION;
D O I
10.4049/jimmunol.1200402
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Differentiation and maintenance of recirculating effector memory CD8 T cells (T-EM) depends on prolonged cognate Ag stimulation. Whether similar pathways of differentiation exist for recently identified tissue-resident effector memory T cells (T-RM), which contribute to rapid local protection upon pathogen re-exposure, is unknown. Memory CD8 alpha beta(+) T cells within small intestine epithelium are well-characterized examples of T-RM, and they maintain a long-lived effector-like phenotype that is highly suggestive of persistent Ag stimulation. This study sought to define the sources and requirements for prolonged Ag stimulation in programming this differentiation state, including local stimulation via cognate or cross-reactive Ags derived from pathogens, microbial flora, or dietary proteins. Contrary to expectations, we found that prolonged cognate Ag stimulation was dispensable for intestinal T-RM ontogeny. In fact, chronic antigenic stimulation skewed differentiation away from the canonical intestinal T cell phenotype. Resident memory signatures, CD69 and CD103, were expressed in many nonlymphoid tissues including intestine, stomach, kidney, reproductive tract, pancreas, brain, heart, and salivary gland and could be driven by cytokines. Moreover, TGF-beta-driven CD103 expression was required for T-RM maintenance within intestinal epithelium in vivo. Thus, induction and maintenance of long-lived effector-like intestinal T-RM differed from classic models of T-EM ontogeny and were programmed through a novel location-dependent pathway that was required for the persistence of local immunological memory. The Journal of Immunology, 2012, 188: 4866-4875.
引用
收藏
页码:4866 / 4875
页数:10
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