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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

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...

【 授权许可】

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