Antigen independent differentiation and maintenance of effector-like resident memory T cells in tissues
By K. Casey, Kathryn A. Fraser, J. Schenkel, Amy E. Moran, Michael C. Abt, Lalit K. Beura, P. Lucas, D. Artis, E. Wherry, K. Hogquist and 2 more. Journal of Immunology, 2012
630 citations recorded by the source corpus.
Differentiation and maintenance of recirculating effector memory CD8 T cells (TEM) depends on prolonged cognate Ag 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 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 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 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 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.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/bf18f510ea4dbfdc1ecd92b6123b651a02a14438
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Citations in the corpus
- Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells (2013, neutral): “…resident memory CD8 T (Trm) cells, which are virusspecific cells that persist in the mucosae and skin after the resolution of viral infections (Casey et al., 2012; Gebhardt et al., 2009; Jiang et al., 2012; Sathaliyawala et al., 2013; Wakim Immunity 38, 1–13, April 18, 2013 ª2013 Elsevier…”
- Tissue-Resident Memory T Cells (2014, background): “Additionally, CD62L cells isolated fromblood and spleen did not recapitulate the panoply of phenotypes expressed by memory T cells isolated from the small intestinal mucosa, lung, and brain (Hawke et al., 1998; Hogan et al., 2001; Kim et al., 1998; Masopust et al., 2001a; van der Most et al., 2003).”
- Quantifying memory CD8 T cells reveals regionalization of immunosurveillance (2015, background): “…a definitive marker to distinguish recirculating cells from TRM. CD69 is known to be induced on TRM precursors upon migration into tissues during the effector phase of immune responses, putatively by tissue-derived instructional cues (Casey et al., 2012; Lee et al., 2011; Masopust et al., 2006;).”