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Role of CD4+ T Cells in the Control of Viral Infections: Recent Advances and Open Questions
Article

CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection

1
INSERM U955, Equipe 16, 94000 Créteil, France
2
Faculté de médecine, Université Paris-Est Créteil, 94000 Créteil, France
3
Vaccine Research Institute (VRI), 94000 Créteil, France
4
Centre for Applied Medical Research, St Vincent’s Hospital, Sydney, NSW 2010, Australia
5
Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
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Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
7
Ramaciotti Facility for Human Systems Biology, The University of Sydney, Sydney, NSW 2006, Australia
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Discipline of Pathology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
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Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC 3010, Australia
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School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
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St Vincent’s Clinical School, St Vincent’s Hospital and University of New South Wales, Sydney, NSW 2052, Australia
12
AP-HP, Hôpital H. Mondor—A. Chenevier, Service d’immunologie Clinique et Maladies Infectieuses, 94000 Créteil, France
*
Authors to whom correspondence should be addressed.
Current address: IDMIT Department/IBFJ, Immunology of Viral Infections and Autoimmune Diseases (IMVA), INSERM U1184, CEA, Université Paris Sud, 92260 Fontenay-aux-Roses, France.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(2), 912; https://doi.org/10.3390/ijms22020912
Received: 5 November 2020 / Revised: 7 January 2021 / Accepted: 12 January 2021 / Published: 18 January 2021
(This article belongs to the Special Issue Recent Advances in T Cell Immunity)
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. View Full-Text
Keywords: CD73; CD4+ subsets; HIV-1 viral reservoir CD73; CD4+ subsets; HIV-1 viral reservoir
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MDPI and ACS Style

Seddiki, N.; Zaunders, J.; Phetsouphanh, C.; Brezar, V.; Xu, Y.; McGuire, H.M.; Bailey, M.; McBride, K.; Hey-Cunningham, W.; Munier, C.M.L.; Cook, L.; Kent, S.; Lloyd, A.; Cameron, B.; Fazekas de St Groth, B.; Koelsch, K.; Danta, M.; Hocini, H.; Levy, Y.; Kelleher, A.D. CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection. Int. J. Mol. Sci. 2021, 22, 912. https://doi.org/10.3390/ijms22020912

AMA Style

Seddiki N, Zaunders J, Phetsouphanh C, Brezar V, Xu Y, McGuire HM, Bailey M, McBride K, Hey-Cunningham W, Munier CML, Cook L, Kent S, Lloyd A, Cameron B, Fazekas de St Groth B, Koelsch K, Danta M, Hocini H, Levy Y, Kelleher AD. CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection. International Journal of Molecular Sciences. 2021; 22(2):912. https://doi.org/10.3390/ijms22020912

Chicago/Turabian Style

Seddiki, Nabila, John Zaunders, Chan Phetsouphanh, Vedran Brezar, Yin Xu, Helen M. McGuire, Michelle Bailey, Kristin McBride, Will Hey-Cunningham, Cynthia M.L. Munier, Laura Cook, Stephen Kent, Andrew Lloyd, Barbara Cameron, Barbara Fazekas de St Groth, Kersten Koelsch, Mark Danta, Hakim Hocini, Yves Levy, and Anthony D. Kelleher. 2021. "CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection" International Journal of Molecular Sciences 22, no. 2: 912. https://doi.org/10.3390/ijms22020912

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