TY - JOUR
T1 - Generation of IL-3–Secreting CD4+ T Cells by Microbial Challenge at Skin and Mucosal Barriers
AU - Kunnath-Velayudhan, Shajo
AU - Goldberg, Michael F.
AU - Saini, Neeraj K.
AU - Ng, Tony W.
AU - Arora, Pooja
AU - Johndrow, Christopher T.
AU - Saavedra-Avila, Noemi Alejandra
AU - Johnson, Alison J.
AU - Xu, Jiayong
AU - Kim, John
AU - Khajoueinejad, Nazanin
AU - Petro, Christopher D.
AU - Herold, Betsy C.
AU - Lauvau, Gregoire
AU - Chan, John
AU - Jacobs, William R.
AU - Porcelli, Steven A.
N1 - Funding Information:
Received for publication April 4, 2019. Accepted for publication April 25, 2019. Address correspondence and reprint requests to: Prof. Steven A. Porcelli, Albert Einstein College of Medicine, Room 416 Forchheimer Building, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail address: steven.porcelli@einstein.yu.edu ORCIDs: 0000-0002-2460-7929 (T.W.N.); 0000-0002-4037-7406 (P.A.); 0000-0002-4441-9888 (S.A.P.). 1Current address: Columbia University, New York, NY. 2Current address: University of Minnesota, Minneapolis, MN. 3Current address: Pfizer Inc., Pearl River, NY. 4Current address: Health Science Communications, New York, NY. 5Current address: Illinois Institute of Technology Research Institute, Chicago, IL. 6Current address: New York Medical College, Valhalla, NY. 7Current address: Regeneron Pharmaceuticals Inc., Tarrytown, NY. This work was supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases Grants 1R21AI092448 (to S.A.P.), 2P01AI063537 (to W.R.J., S.A.P., and J.C.), AI26170 (to W.R.J.), AI117321 (to W.R.J. and B.C.H.), and U19AI03461 (to B.C.H.). Core resource for flow cytometry was supported by the Einstein Cancer Center under NIH Grant P30 CA13330. Support for C.T.J. was provided by NIH Training Grant GM07491. Abbreviations used in this article: BCG, bacillus Calmette-Guerin; iTreg, induced regulatory T; LLO, listeriolysin O; MHC II, MHC class II; Tg, transgenic; WT, wild-type. The online version of this article contains supplemental material. This article is distributed under the terms of the CC BY 4.0 Unported license. Copyright © 2019 The Authors
Publisher Copyright:
Copyright © 2019 The Authors
PY - 2019/5/1
Y1 - 2019/5/1
N2 - During Ag priming, naive CD4+ T cells differentiate into subsets with distinct patterns of cytokine expression that dictate to a major extent their functional roles in immune responses. We identified a subset of CD4+ T cells defined by secretion of IL-3 that was induced by Ag stimulation under conditions different from those associated with previously defined functional subsets. Using mouse models of bacterial and viral infections, we showed that IL-3–secreting CD4+ T cells were generated by infection at the skin and mucosa but not by infections introduced directly into the blood. Most IL-3–producing T cells coexpressed GM-CSF and other cytokines that define multifunctionality. Generation of IL-3–secreting T cells in vitro was dependent on IL-1 family cytokines and was inhibited by cytokines that induce canonical Th1 or Th2 cells. Our results identify IL-3–secreting CD4+ T cells as a potential functional subset that arises during priming of naive T cells in specific tissue locations.
AB - During Ag priming, naive CD4+ T cells differentiate into subsets with distinct patterns of cytokine expression that dictate to a major extent their functional roles in immune responses. We identified a subset of CD4+ T cells defined by secretion of IL-3 that was induced by Ag stimulation under conditions different from those associated with previously defined functional subsets. Using mouse models of bacterial and viral infections, we showed that IL-3–secreting CD4+ T cells were generated by infection at the skin and mucosa but not by infections introduced directly into the blood. Most IL-3–producing T cells coexpressed GM-CSF and other cytokines that define multifunctionality. Generation of IL-3–secreting T cells in vitro was dependent on IL-1 family cytokines and was inhibited by cytokines that induce canonical Th1 or Th2 cells. Our results identify IL-3–secreting CD4+ T cells as a potential functional subset that arises during priming of naive T cells in specific tissue locations.
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U2 - 10.4049/immunohorizons.1900028
DO - 10.4049/immunohorizons.1900028
M3 - Article
C2 - 31356170
AN - SCOPUS:85079664394
SN - 2573-7732
VL - 3
SP - 161
EP - 171
JO - ImmunoHorizons
JF - ImmunoHorizons
IS - 5
ER -