title: Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection.
abstract: Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved antimicrobial MR1-restricted T-cell subset. MAIT cells are CD161(+), express a V7.2 TCR, are primarily CD8(+) and numerous in blood and mucosal tissues. However, their role in HIV-1 infection is unknown. In this study, we found levels of MAIT cells to be severely reduced in circulation in patients with chronic HIV-1 infection. Residual MAIT cells were highly activated and functionally exhausted. Their decline was associated with time since diagnosis, activation levels, and the concomitant expansion of a subset of functionally impaired CD161(+) V7.2(+) T cells. Such cells were generated in vitro by exposure of MAIT cells to Escherichia coli. Notably, whereas the function of residual MAIT cells was at least partly restored by effective antiretroviral therapy, levels of MAIT cells in peripheral blood were not restored. Interestingly, MAIT cells in rectal mucosa were relatively preserved, although some of the changes seen in blood were recapitulated in the mucosa. These findings are consistent with a model in which the MAIT-cell compartment, possibly as a result of persistent exposure to microbial material, is engaged, activated, exhausted, and progressively and persistently depleted during chronic HIV-1 infection.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. edwin.leeansyah@ki.se
authors.forename: Edwin
authors.initials: E
authors.lastname: Leeansyah
authors.forename: Anupama
authors.initials: A
authors.lastname: Ganesh
authors.forename: Máire F
authors.initials: MF
authors.lastname: Quigley
authors.forename: Anders
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Ma
authors.initials: M
authors.lastname: Somsouk
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Markus
authors.initials: M
authors.lastname: Moll
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Shacklett
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology
chemical_list: D015395:Histocompatibility Antigens Class I; C527203:KLRB1 protein, human; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell