Mucosa-associated invariant T cells are systemically depleted in simian immunodeficiency virus-infected rhesus macaques

Other literature type, Article English OPEN
Vinton, Carol ; Wu, Fan ; Rossjohn, Jamie ; Matsuda, Kenta ; McCluskey, James ; Hirsch, Vanessa ; Price, David ; Brenchley, Jason M. ; Silvestri, G. (2016)
  • Publisher: American Society for Microbiology
  • Related identifiers: doi: 10.1128/JVI.02876-15
  • Subject: Pathogenesis and Immunity

Mucosa-associated invariant T (MAIT) cells contribute to host immune protection against a wide range of potential pathogens via the recognition of bacterial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although bacterial products translocate systemically in human immunodeficiency virus (HIV)-infected individuals and simian immunodeficiency virus (SIV)-infected Asian macaques, several studies have shown that MAIT cell frequencies actually decrease in peripheral blood during the course of HIV/SIV disease. However, the mechanisms underlying this proportional decline remain unclear. In this study, we characterized the phenotype, activation status, functionality, distribution, and clonotypic structure of MAIT cell populations in the peripheral blood, liver, mesenteric lymph nodes (MLNs), jejunum, and bronchoalveolar lavage (BAL) fluid of healthy and SIV-infected rhesus macaques (RMs). Low frequencies of MAIT cells were observed in the peripheral blood, MLNs, and BAL fluid of SIV-infected RMs. These numerical changes were coupled with increased proliferation and a highly public T cell receptor alpha (TCRα) repertoire in the MAIT cell compartment without redistribution to other anatomical sites. Collectively, our data show systemically decreased frequencies of MAIT cells likely attributable to enhanced turnover in SIV-infected RMs. This process may impair protective immunity against certain opportunistic infections with progression to AIDS.
  • References (39)
    39 references, page 1 of 4

    1. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, Affaticati P, Gilfillan S, Lantz O. 2003. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164 -169. http://dx.doi.org/10.1038/nature01433.

    2. Le Bourhis L, Martin E, Peguillet I, Guihot A, Froux N, Core M, Levy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O. 2010. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11:701- 708. http://dx.doi.org/10.1038/ni.1890.

    3. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C, Premel V, Devys A, Moura IC, Tilloy F, Cherif S, Vera G, Latour S, Soudais C, Lantz O. 2009. Stepwise development of MAIT cells in mouse and human. PLoS Biol 7:e54. http://dx.doi.org/10.1371/journal.pbio.1000054.

    4. Dusseaux M, Martin E, Serriari N, Peguillet I, Premel V, Louis D, Milder M, Le Bourhis L, Soudais C, Treiner E, Lantz O. 2011. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17- secreting T cells. Blood 117:1250 -1259. http://dx.doi.org/10.1182/blood -2010-08-303339.

    5. Gold MC, Lewinsohn DM. 2013. Co-dependents: MR1-restricted MAIT cells and their antimicrobial function. Nat Rev Microbiol 11:14 -19. http: //dx.doi.org/10.1038/nrmicro2918.

    6. Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Chen Z, Eckle SB, Uldrich AP, Birkinshaw RW, Patel O, Kostenko L, Meehan B, Kedzierska K, Liu L, Fairlie DP, Hansen TH, Godfrey DI, Rossjohn J, McCluskey J, Kjer-Nielsen L. 2013. Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J Exp Med 210:2305-2320. http://dx.doi.org/10.1084/jem.20130958.

    7. Tilloy F, Treiner E, Park SH, Garcia C, Lemonnier F, de la Salle H, Bendelac A, Bonneville M, Lantz O. 1999. An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammals. J Exp Med 189:1907-1921. http://dx.doi.org/10.1084/jem.189.12.1907.

    8. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O'Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J. 2012. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491:717-723. http://dx.doi .org/10.1038/nature11605.

    9. Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J, Winata E, Swarbrick GM, Chua WJ, Yu YY, Lantz O, Cook MS, Null MD, Jacoby DB, Harriff MJ, Lewinsohn DA, Hansen TH, Lewinsohn DM. 2010. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol 8:e1000407. http://dx.doi.org/10.1371/journal .pbio.1000407.

    10. Gold MC, McLaren JE, Reistetter JA, Smyk-Pearson S, Ladell K, Swarbrick GM, Yu YY, Hansen TH, Lund O, Nielsen M, Gerritsen B, Kesmir C, Miles JJ, Lewinsohn DA, Price DA, Lewinsohn DM. 2014. MR1- restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. J Exp Med 211:1601-1610. http: //dx.doi.org/10.1084/jem.20140507.

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