title: Functional role of mucosal-associated invariant T cells in HIV infection.
abstract: MAIT cells represent an evolutionarily conserved, MR1-restricted, innate-like cell subset that express high levels of CD161; have a canonical semi-invariant TCR iVα7.2; and may have an important role in mucosal immunity against various bacterial and fungal pathogens. Mature MAIT cells are CD161(hi)PLZF(hi)IL-18Rα(+)iVα7.2(+)γδ-CD3(+)CD8(+) T cells and occur in the peripheral blood, liver, and mucosa of humans. MAIT cells are activated by a metabolic precursor of riboflavin synthesis presented by MR1 and, therefore, respond to many bacteria and some fungi. Despite their broad antibacterial properties, their functional role in persistent viral infections is poorly understood. Although there is an increasing line of evidence portraying the depletion of MAIT cells in HIV disease, the magnitude and the potential mechanisms underlying such depletion remain unclear. Recent studies suggest that MAIT cells are vulnerable to immune exhaustion as a consequence of HIV and hepatitis C virus infections and HIV/tuberculosis coinfections. HIV infection also appears to cause functional depletion of MAIT cells resulting from abnormal expression of T-bet and EOMES, and effective ART is unable to completely salvage functional MAIT cell loss. Depletion and exhaustion of peripheral MAIT cells may affect mucosal immunity and could increase susceptibility to opportunistic infections during HIV infection. Here, we review some of the important mechanisms associated with depletion and functional loss of MAIT cells and also suggest potential immunotherapeutic strategies to restore MAIT cell functions, including the use of IL-7 to restore effector functions in HIV disease.
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia; Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia;
authors.forename: Alireza
authors.initials: A
authors.lastname: Saeidi
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;
authors.forename: Rada
authors.initials: R
authors.lastname: Ellegård
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia;
authors.forename: Yean K
authors.initials: YK
authors.lastname: Yong
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia;
authors.forename: Hong Y
authors.initials: HY
authors.lastname: Tan
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Georgia, Atlanta, USA; and.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: James E
authors.initials: JE
authors.lastname: Ussher
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia; Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia; shankarem@um.edu.my.
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
mesh_terms: D000818:Animals; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology*
keywords: CD8+ T cells; PD-1; TCR iVα7.2; cytotoxicity; exhaustion