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Staged development of long-lived T-cell receptor αβ TH17 resident memory T-cell population to Candida albicans after skin infection

Authors
 Chang Ook Park  ;  Xiujun Fu  ;  Xiaodong Jiang  ;  Youdong Pan  ;  Jessica E. Teague  ;  Nicholas Collins  ;  Tian Tian  ;  John T. O'Malley  ;  Ryan O. Emerson  ;  Ji Hye Kim  ;  Yookyung Jung  ;  Rei Watanabe  ;  Robert C. Fuhlbrigge  ;  Francis R. Carbone  ;  Thomas Gebhardt  ;  Rachael A. Clark  ;  Charles P. Lin  ;  Thomas S. Kupper 
Citation
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol.142(2) : 647-662, 2018 
Journal Title
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 
ISSN
 0091-6749 
Issue Date
2018
Keywords
CD4(+) T(RM) ; Candida albicans ; IL-17 ; Resident memory T cells ; T(H)17 ; T(RM)
Abstract
BACKGROUND: Candida albicans is a dimorphic fungus to which human subjects are exposed early in life, and by adulthood, it is part of the mycobiome of skin and other tissues. Neonatal skin lacks resident memory T (TRM) cells, but in adults the C albicans skin test is a surrogate for immunocompetence. Young adult mice raised under specific pathogen-free conditions are naive to C albicans and have been shown recently to have an immune system resembling that of neonatal human subjects. OBJECTIVE: We studied the evolution of the adaptive cutaneous immune response to Candida species. METHODS: We examined both human skin T cells and the de novo and memory immune responses in a mouse model of C albicans skin infection. RESULTS: In mice the initial IL-17-producing cells after C albicans infection were dermal γδ T cells, but by day 7, αβ TH17 effector T cells were predominant. By day 30, the majority of C albicans-reactive IL-17-producing T cells were CD4 TRM cells. Intravital microscopy showed that CD4 effector T cells were recruited to the site of primary infection and were highly motile 10 days after infection. Between 30 and 90 days after infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established TRM cells produced IL-17 on challenge, whereas motile migratory memory T cells did not. TRM cells rapidly clear an infectious challenge with C albicans more effectively than recirculating T cells, although both populations participate. We found that in normal human skin IL-17-producing CD4+ TRM cells that responded to C albicans in an MHC class II-restricted fashion could be identified readily. CONCLUSIONS: These studies demonstrate that C albicans infection of skin preferentially generates CD4+ IL-17-producing TRM cells, which mediate durable protective immunity.
Full Text
https://www.sciencedirect.com/science/article/pii/S0091674917317372
DOI
10.1016/j.jaci.2017.09.042
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Park, Chang Ook(박창욱) ORCID logo https://orcid.org/0000-0003-3856-1201
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161627
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