BioAcyl Corp
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Casey, K. A., Fraser, K. A., Schenkel, J. M., Moran, A., Abt, M. C., & Beura, L. K., et al. (2012). Antigen independent differentiation and maintenance of effector-like resident memory T cells in tissues. Journal of immunology (Baltimore, Md. : 1950), 188(10), 4866. Added by: Dr. Enrique Feoli (03/10/2020, 15:47) Last edited by: Dr. Enrique Feoli (03/10/2020, 15:50) |
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| Resource type: Journal Article DOI: 10.4049/jimmunol.1200402 BibTeX citation key: Casey2012 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: COVID-19 Tcell memory Creators: Abt, Artis, Beura, Casey, Fraser, Hogquist, Lucas, Masopust, Moran, Schenkel, Vezys, Wherry Collection: Journal of immunology (Baltimore, Md. : 1950) |
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| Abstract |
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Differentiation and maintenance of recirculating effector memory CD8 T cells (TEM) depends on prolonged cognate antigen stimulation. Whether similar pathways of differentiation exist for recently identified tissue-resident effector memory T cells (TRM), 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 TRM and they maintain a long-lived effector-like phenotype that is highly suggestive of persistent antigen 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 antigens derived from pathogens, microbial flora, or dietary proteins. Contrary to expectations, we found that prolonged cognate Ag-stimulation was dispensable for intestinal TRM 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 non-lymphoid tissues including intestine, stomach, kidney, reproductive tract, pancreas, brain, heart, and salivary gland, and could be driven by cytokines. Moreover, TGFβ driven CD103 expression was required for TRM maintenance within intestinal epithelium in vivo. Thus, induction and maintenance of long-lived effector-like intestinal TRM 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.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |