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

• Published in: Blood Vol. 120; no. 17; pp. 3466 - 3477
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 25.10.2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Acute Disease; Antibody-Dependent Cell Cytotoxicity - genetics; Antibody-Dependent Cell Cytotoxicity - immunology; Apoptosis; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Proliferation; Chronic Disease; Gene Expression Regulation - immunology; Hematologic and hematopoietic diseases; HIV - physiology; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - pathology; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Immunobiology; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Medical sciences; Receptors, Interleukin-7 - genetics; Receptors, Interleukin-7 - immunology; Time Factors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Immunopathology; Cytolysis; Hematology; Primary infection; Retroviridae; AIDS; Metabolism; Immune deficiency; Lentivirus; Infection; Virus; Chronic; Viral disease; Human immunodeficiency virus; CD8 T lymphocyte
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-04-422550

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.