Antigen-independent differentiation and maintenance of effector-like resident memory T Cells in tissues

Kerry A. Casey, Kathryn A. Fraser, Jason M. Schenkel, Amy Moran, Michael C. Abt, Lalit K. Beura, Philip J. Lucas, David Artis, E. John Wherry, Kristin Hogquist, Vaiva Vezys, David Masopust

Research output: Contribution to journalArticle

254 Citations (Scopus)

Abstract

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 CD8αβ+ 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- β-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 TEM ontogeny and were programmed through a novel location-dependent pathway that was required for the persistence of local immunological memory.

Original languageEnglish (US)
Pages (from-to)4866-4875
Number of pages10
JournalJournal of Immunology
Volume188
Issue number10
DOIs
StatePublished - May 15 2012
Externally publishedYes

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Differentiation Antigens
Maintenance
T-Lymphocytes
Immunologic Memory
Phenotype
Dietary Proteins
Intestinal Mucosa
Salivary Glands
Small Intestine
Intestines
Pancreas
Stomach
Epithelium
Cytokines
Kidney
Brain

ASJC Scopus subject areas

  • Immunology

Cite this

Casey, K. A., Fraser, K. A., Schenkel, J. M., Moran, A., Abt, M. C., Beura, L. K., ... Masopust, D. (2012). Antigen-independent differentiation and maintenance of effector-like resident memory T Cells in tissues. Journal of Immunology, 188(10), 4866-4875. https://doi.org/10.4049/jimmunol.1200402

Antigen-independent differentiation and maintenance of effector-like resident memory T Cells in tissues. / Casey, Kerry A.; Fraser, Kathryn A.; Schenkel, Jason M.; Moran, Amy; Abt, Michael C.; Beura, Lalit K.; Lucas, Philip J.; Artis, David; Wherry, E. John; Hogquist, Kristin; Vezys, Vaiva; Masopust, David.

In: Journal of Immunology, Vol. 188, No. 10, 15.05.2012, p. 4866-4875.

Research output: Contribution to journalArticle

Casey, KA, Fraser, KA, Schenkel, JM, Moran, A, Abt, MC, Beura, LK, Lucas, PJ, Artis, D, Wherry, EJ, Hogquist, K, Vezys, V & Masopust, D 2012, 'Antigen-independent differentiation and maintenance of effector-like resident memory T Cells in tissues', Journal of Immunology, vol. 188, no. 10, pp. 4866-4875. https://doi.org/10.4049/jimmunol.1200402
Casey, Kerry A. ; Fraser, Kathryn A. ; Schenkel, Jason M. ; Moran, Amy ; Abt, Michael C. ; Beura, Lalit K. ; Lucas, Philip J. ; Artis, David ; Wherry, E. John ; Hogquist, Kristin ; Vezys, Vaiva ; Masopust, David. / Antigen-independent differentiation and maintenance of effector-like resident memory T Cells in tissues. In: Journal of Immunology. 2012 ; Vol. 188, No. 10. pp. 4866-4875.
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