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广东快乐十分中奖直三:Regulatory T cells limit unconventional memory to preserve the capacity to mount protective CD8 memory responses to pathogens
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T cell-mediated immune memory provides the host with the capacity to rapidly and efficiently respond to pathogen reencounter, often without symptoms or disease. In addition to conventional memory T cell responses that are pathogen-specific, there also exists a subset of unconventional memory T cells that share many of the characteristics of conventional memory T cells without the initiating requirement of cognate antigen recognition. Here, we demonstrate a mechanism whereby regulatory T cells limit the expansion of these unconventional memory T cells to preserve a host’s capacity to mount a memory CD8 T cell response that remains protective upon pathogen reencounter.
Immunological memory exists so that following infection an expanded population of pathogen-specific lymphocytes can rapidly and efficiently control infection in the case of reexposure. However, in the case of CD8+ T lymphocytes, a population of unconventional CD44+CD122+ virtual memory T cells (TVM) has been described that possesses many, though not all, features of “true memory” T cells, without the requirement of first encountering cognate antigen. Here, we demonstrate a role for regulatory T cell-mediated restraint of TVM at least in part through limiting IL-15 trans-presentation by CD11b+ dendritic cells. Further, we show that keeping TVM in check ensures development of functional, antigen-specific “true” memory phenotype CD8+ T cells that can assist in pathogen control upon reexposure.
?1A.S.D.C. and J.B.G. contributed equally to this work.
- ?2To whom correspondence should be addressed. Email: .
Author contributions: A.S.D.C., J.B.G., and J.M.L. designed research; A.S.D.C., J.B.G., and J.L.S. performed research; A.S.D.C., J.B.G., J.L.S., and J.M.L. analyzed data; and A.S.D.C., J.B.G., and J.M.L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1818327116/-/DCSupplemental.
Published under the PNAS license.