Functional role of mucosal‐associated invariant T cells in HIV infection

[摘要] MAITcellsrepresentanevolutionarilyconserved,MR1‐restricted,innate‐likecellsubsetthatexpresshighlevelsofCD161;haveacanonicalsemi‐invariantTCRiVα7.2;andmayhaveanimportantroleinmucosalimmunityagainstvariousbacterialandfungalpathogens.MatureMAITcellsareCD161hiPLZFhiIL‐18Rα+iVα7.2+γδ‐CD3+CD8+Tcellsandoccurintheperipheralblood,liver,andmucosaofhumans.MAITcellsareactivatedbyametabolicprecursorofriboflavinsynthesispresentedbyMR1and,therefore,respondtomanybacteriaandsomefungi.Despitetheirbroadantibacterialproperties,theirfunctionalroleinpersistentviralinfectionsispoorlyunderstood.AlthoughthereisanincreasinglineofevidenceportrayingthedepletionofMAITcellsinHIVdisease,themagnitudeandthepotentialmechanismsunderlyingsuchdepletionremainunclear.RecentstudiessuggestthatMAITcellsarevulnerabletoimmuneexhaustionasaconsequenceofHIVandhepatitisCvirusinfectionsandHIV/tuberculosiscoinfections.HIVinfectionalsoappearstocausefunctionaldepletionofMAITcellsresultingfromabnormalexpressionofT‐betandEOMES,andeffectiveARTisunabletocompletelysalvagefunctionalMAITcellloss.DepletionandexhaustionofperipheralMAITcellsmayaffectmucosalimmunityandcouldincreasesusceptibilitytoopportunisticinfectionsduringHIVinfection.Here,wereviewsomeoftheimportantmechanismsassociatedwithdepletionandfunctionallossofMAITcellsandalsosuggestpotentialimmunotherapeuticstrategiestorestoreMAITcellfunctions,includingtheuseofIL‐7torestoreeffectorfunctionsinHIVdisease...

[学科分类] 生理学

[关键词] CD8+ T cells;cytotoxicity;exhaustion;PD‐1;TCR iVα7.2