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Tytuł pozycji:

CD73 + CD127 high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection.

Tytuł :
CD73 Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection.
Autorzy :
Seddiki N; INSERM U955, Equipe 16, 94000 Créteil, France.; Faculté de médecine, Université Paris-Est Créteil, 94000 Créteil, France.; Vaccine Research Institute (VRI), 94000 Créteil, France.
Zaunders J; Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW 2010, Australia.; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Phetsouphanh C; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Brezar V; INSERM U955, Equipe 16, 94000 Créteil, France.
Xu Y; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
McGuire HM; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.; Ramaciotti Facility for Human Systems Biology, The University of Sydney, Sydney, NSW 2006, Australia.; Discipline of Pathology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Bailey M; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
McBride K; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Hey-Cunningham W; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Munier CML; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Cook L; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Kent S; Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC 3010, Australia.
Lloyd A; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Cameron B; School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Fazekas de St Groth B; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.; Ramaciotti Facility for Human Systems Biology, The University of Sydney, Sydney, NSW 2006, Australia.; Discipline of Pathology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Koelsch K; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Danta M; St Vincent's Clinical School, St Vincent's Hospital and University of New South Wales, Sydney, NSW 2052, Australia.
Hocini H; INSERM U955, Equipe 16, 94000 Créteil, France.
Levy Y; INSERM U955, Equipe 16, 94000 Créteil, France.; Faculté de médecine, Université Paris-Est Créteil, 94000 Créteil, France.; Vaccine Research Institute (VRI), 94000 Créteil, France.; AP-HP, Hôpital H. Mondor-A. Chenevier, Service d'immunologie Clinique et Maladies Infectieuses, 94000 Créteil, France.
Kelleher AD; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
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Źródło :
International journal of molecular sciences [Int J Mol Sci] 2021 Jan 18; Vol. 22 (2). Date of Electronic Publication: 2021 Jan 18.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms :
Molecular Targeted Therapy*
Antigens, CD/*immunology
Cell Proliferation/*genetics
HIV Infections/*genetics
5'-Nucleotidase/genetics ; 5'-Nucleotidase/immunology ; Antigens, CD/genetics ; Antigens, CD/therapeutic use ; Cell Lineage/genetics ; Cell Lineage/immunology ; HIV Infections/immunology ; HIV Infections/pathology ; HIV Infections/virology ; HIV-1/immunology ; HIV-1/pathogenicity ; Humans ; Interleukin-7 Receptor alpha Subunit/genetics ; Interleukin-7 Receptor alpha Subunit/immunology ; Memory, Long-Term/physiology
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Grant Information :
1063422 National Health and Medical Research Council; 1052979 National Health and Medical Research Council; 1037298 National Health and Medical Research Council
Contributed Indexing :
Keywords: CD4+ subsets; CD73; HIV-1 viral reservoir
Substance Nomenclature :
0 (Antigens, CD)
0 (Interleukin-7 Receptor alpha Subunit)
EC 3.1.3.5 (5'-Nucleotidase)
Entry Date(s) :
Date Created: 20210122 Date Completed: 20210907 Latest Revision: 20210907
Update Code :
20210914
PubMed Central ID :
PMC7831934
DOI :
10.3390/ijms22020912
PMID :
33477692
Czasopismo naukowe
HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4+ T cells in peripheral blood, which highly express the α-chain of the IL-7 receptor (CD127), but not CD38 or Ki-67, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease very early in HIV-1 infection. Indeed, CD73+ memory CD4+ T cells comprised a median of 7.5% (interquartile range: 4.5-10.4%) of CD4+ T cells in peripheral blood from healthy adults, but were decreased in primary HIV-1 infection to a median of 3.7% (IQR: 2.6-6.4%; p = 0.002); and in chronic HIV-1 infection to 1.9% (IQR: 1.1-3%; p < 0.0001), and were not restored by antiretroviral therapy. Moreover, we found that a significant proportion of CD73+ memory CD4+ T cells were skewed to a gut-homing phenotype, expressing integrins α4 and β7, CXCR3, CCR6, CD161 and CD26. Accordingly, 20% of CD4+ T cells present in gut biopsies were CD73+. In HIV+ subjects, purified CD73+ resting memory CD4+ T cells in PBMC were infected with HIV-1 DNA, determined by real-time PCR, to the same level as for purified CD73-negative CD4+ T cells, both in untreated and treated subjects. Therefore, the proliferative CD73+ subset of memory CD4+ T cells is disproportionately reduced in HIV-1 infection, but, unexpectedly, their IL-7 dependent long-term resting phenotype suggests that residual infected cells in this subset may contribute significantly to the very long-lived HIV proviral DNA reservoir in treated subjects.
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