Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection
Cormac Cosgrove, James E Ussher, Andri Rauch, Kathleen Gärtner, Ayako Kurioka, Michael H Hühn, Krista Adelmann, Yu-Hoi Kang, Joannah R Fergusson, Peter Simmonds, Philip Goulder, Ted H Hansen, Julie Fox, Huldrych F Günthard, Nina Khanna, Fiona Powrie, Alan Steel, Brian Gazzard, Rodney E Phillips, John Frater, Holm Uhlig, Paul Klenerman, Cormac Cosgrove, James E Ussher, Andri Rauch, Kathleen Gärtner, Ayako Kurioka, Michael H Hühn, Krista Adelmann, Yu-Hoi Kang, Joannah R Fergusson, Peter Simmonds, Philip Goulder, Ted H Hansen, Julie Fox, Huldrych F Günthard, Nina Khanna, Fiona Powrie, Alan Steel, Brian Gazzard, Rodney E Phillips, John Frater, Holm Uhlig, Paul Klenerman
Abstract
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, IFN, 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.
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Source: PubMed