Early and nonreversible decrease of CD161++/MAIT cells in HIV infection

• Published in: Blood 2013-02, Vol.121 (6), p.951-961
• Main Authors: Cosgrove, Cormac, Ussher, James E., Rauch, Andri, Gärtner, Kathleen, Kurioka, Ayako, Hühn, Michael H., Adelmann, Krista, Kang, Yu-Hoi, Fergusson, Joannah R., Simmonds, Peter, Goulder, Philip, Hansen, Ted H., Fox, Julie, Günthard, Huldrych F., Khanna, Nina, Powrie, Fiona, Steel, Alan, Gazzard, Brian, Phillips, Rodney E., Frater, John, Uhlig, Holm, Klenerman, Paul
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Apoptosis - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - virology; Cells, Cultured; Cohort Studies; Escherichia coli - immunology; Female; Flow Cytometry; HIV - drug effects; HIV - immunology; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - immunology; Humans; Immunity, Mucosal - immunology; Immunobiology; Immunohistochemistry; Interleukin-17 - immunology; Interleukin-17 - metabolism; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - virology; Lymphocyte Count; Male; Middle Aged; NK Cell Lectin-Like Receptor Subfamily B - immunology; NK Cell Lectin-Like Receptor Subfamily B - metabolism; Receptors, CCR5 - immunology; Receptors, CCR5 - metabolism; Receptors, CCR6 - immunology; Receptors, CCR6 - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - virology; Time Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-06-436436

HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFNγ, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++/MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++/MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++/MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV. •The frequency of CD161++ MAIT cells is dramatically decreased in the blood of HIV-infected patients, and they are nonrecoverable with HAART.•Gut sequestration and apoptosis in response to bacterial signals may, amongst others, be mechanisms that contribute to this.