Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection

Lydie Trautmann, Florentin Martial Mbitikon-Kobo, Jean Philippe Goulet, Yoav Peretz, Yu Shi, Julien Van Grevenynghe, Francesco Andrea Procopio, Mohamad Rachid Boulassel, Jean Pierre Routy, Nicolas Chomont, Elias K. Haddad, Rafick Pierre Sekaly

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Immediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.

Original languageEnglish
Pages (from-to)3466-3477
Number of pages12
JournalBlood
Volume120
Issue number17
DOIs
Publication statusPublished - Oct 25 2012

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T-cells
HIV Infections
HIV
T-Lymphocytes
Infection
Functional analysis
Viruses
Gene expression
Interleukin-2
Disease Progression
Maintenance
Apoptosis
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Trautmann, L., Mbitikon-Kobo, F. M., Goulet, J. P., Peretz, Y., Shi, Y., Van Grevenynghe, J., ... Sekaly, R. P. (2012). Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection. Blood, 120(17), 3466-3477. https://doi.org/10.1182/blood-2012-04-422550

Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection. / Trautmann, Lydie; Mbitikon-Kobo, Florentin Martial; Goulet, Jean Philippe; Peretz, Yoav; Shi, Yu; Van Grevenynghe, Julien; Procopio, Francesco Andrea; Boulassel, Mohamad Rachid; Routy, Jean Pierre; Chomont, Nicolas; Haddad, Elias K.; Sekaly, Rafick Pierre.

In: Blood, Vol. 120, No. 17, 25.10.2012, p. 3466-3477.

Research output: Contribution to journalArticle

Trautmann, L, Mbitikon-Kobo, FM, Goulet, JP, Peretz, Y, Shi, Y, Van Grevenynghe, J, Procopio, FA, Boulassel, MR, Routy, JP, Chomont, N, Haddad, EK & Sekaly, RP 2012, 'Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection', Blood, vol. 120, no. 17, pp. 3466-3477. https://doi.org/10.1182/blood-2012-04-422550
Trautmann, Lydie ; Mbitikon-Kobo, Florentin Martial ; Goulet, Jean Philippe ; Peretz, Yoav ; Shi, Yu ; Van Grevenynghe, Julien ; Procopio, Francesco Andrea ; Boulassel, Mohamad Rachid ; Routy, Jean Pierre ; Chomont, Nicolas ; Haddad, Elias K. ; Sekaly, Rafick Pierre. / Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection. In: Blood. 2012 ; Vol. 120, No. 17. pp. 3466-3477.
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