Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Functional role of mucosal‐associated invariant T cells in HIV infection | |
关键词: CD8+ T cells; cytotoxicity; exhaustion; PD‐; 1; TCR iVα; 7.2; | |
DOI : 10.1189/jlb.4RU0216-084R | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 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...
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