CD4+CD28null T lymphocytes resemble CD8+CD28null T lymphocytes in their responses to IL‐15 and IL‐21 in HIV‐infected patients

摘要

HIV‐infectedindividualssufferfromacceleratedimmunologicaging.OneofthemostprominentchangesduringTlymphocyteagingistheaccumulationofCD28nullTlymphocytes,mainlyCD8+butalsoCD4+Tlymphocytes.Enhancingthefunctionalpropertiesofthesecellsmaybeimportantbecausetheyprovideantigen‐specificdefenseagainstchronicinfections.TheobjectiveofthisstudywastocomparetheresponsesofCD4+CD28nullandCD8+CD28nullTlymphocytesfromHIV‐infectedpatientstotheimmunomodulatoryeffectsofcytokinesIL‐15andIL‐21.WequantifiedthefrequenciesofCD4+CD28nullandCD8+CD28nullTlymphocytesinperipheralbloodfrom110consecutive,HIV‐infectedpatientsand25healthycontrols.PatientsshowedincreasedfrequenciesofCD4+CD28nullandCD8+CD28null.BothsubsetswerepositivelycorrelatedtoeachotherandshowedaninversecorrelationwiththeabsolutecountsofCD4+Tlymphocytes.HigherfrequenciesofHIV‐specificandCMV‐specificcellswerefoundinCD28nullthaninCD28+Tlymphocytes.ActivationofSTAT5byIL‐15andSTAT3byIL‐21washigherinCD28nullcomparedwithCD28+Tlymphocytes.Proliferation,expressionofCD69,andIFN‐γproductioninCD28nullTlymphocyteswereincreasedaftertreatmentwithIL‐15,andIL‐21potentiatedmostofthoseeffects.Nevertheless,IL‐21alonereducedIFN‐γproductioninresponsetoanti‐CD3stimulationbutincreasedCD28expression,evencounteractingtheinhibitoryeffectofIL‐15.IntracytoplasmicstoresofgranzymeBandperforinwereincreasedbyIL‐15,whereasIL‐21andsimultaneoustreatmentwiththe2cytokinesalsosignificantlyenhanceddegranulationinCD4+CD28nullandCD8+CD28nullTlymphocytes.IL‐15andIL‐21couldhavearoleinenhancingtheeffectorresponseofCD28nullTlymphocytesagainsttheirspecificchronicantigensinHIV‐infectedpatients...