人类免疫缺陷病毒感染患者中淋巴因子基因表达的动态变化

TheKineticsofCytokineGeneExpressioninPBMCfromHIVSeropositiveSubjectsStimulatedbyPhy-tohaemagglutinin,PokeweedMitogen,Candidin,Anti-CD3MonoclonalAntibodyandRecombinantIL-2

在感染性疾病中，淋巴因子与免疫调节机制密切相关。为了解在人类免疫缺陷病毒（ＨＩＶ）感染患者中淋巴因子对多种刺激原的动态变化反应情况，以便进一步弄清ＨＩＶ感染的病理变化机制，我们采用定量逆转录聚合酶链反应的方法（ＲＴ－ＰＣＲ），对经植物血凝素（ＰＨＡ）、商陆致丝裂素（ＰＷＭ）、念珠菌蛋白（ｃａｎｄｉｄｉｎ）、抗ＣＤ３单克隆抗体（Ａｎｔｉ－ＣＤ３ＭＡｂ）和重组白介素２（ｒＩＬ２）刺激后的ＨＩＶ感染者及对照组外周血单一核细胞（ＰＢＭＣ）中的白介素２（ＩＬ２）、γ干扰素（ＩＦＮ－γ）、白介素１０（ＩＬ１０）、白介素６（ＩＬ６）、肿瘤坏死因子α（ＴＮＦ－α）和ＩＬ２受体（ＩＬ２Ｒ）的动态变化进行了比较。在ＨＩＶ感染组中，其ＩＬ２和ＩＬ２Ｒ基因表达水平明显低于对照组。ＩＬ２和ＩＦＮ－γ均由Ｔ辅助细胞一型（ＴＨ１）克隆产生，然而在ＨＩＶ感染患者中，ＩＦＮ－γ的水平却明显增高。ＩＬ１０基因表达情况视刺激原的不同而不同。经ＰＨＡ、ｃａｎｄｉｄｉｎ、ｒＩＬ２（１０００Ｕ）刺激后，ＨＩＶ感染组ＩＬ１０ｍＲＮＡ表达水平明显高于对照组，但经ｒＩＬ２（１０Ｕ）和Ａｎｔｉ－ＣＤ３ＭＡｂ刺激后却低于对照组。ＨＩＶ感染组ＴＮＦ－α基因表达开?

Cytokineswerecloselyrelatedtothemajorimmunoregulatorymechanismininfectiousdisease.ThekineticsofcytokinegeneexpressionsincludingIL-2,IFN-γ,IL-10,IL-6,TNF-αandIL-2receptorinPBMCfromHIVseropositiveandseronegativesubjectswerecomparedbyquantitativere-versetranscriptionpolymerasechainreactionstudiesstimulatedbyphytohaemaglutinin(PHA),poke-wedmitogen(PWM),candidin,anti-CD3monoclonalantibody(Anti-CD3mAb)andrecombinantIL-2(rIL-2).IL-2andIL-2receptor(IL-2R)toPHA,PWM,candidin,anti-CD3mAbandrIL-2stimulationweremarkedlyloweredinpatientswithHIVinfection.ItisknownthatTh1cloneproducesIL-2andIFN-γ,however,highlevelofINF-γgeneexpressionwasfoundinthePBMCofpatientswithHIVin-fectionstimulatedbyPHA,candidin,PWM,10unitsofrIL-2andanti-CD3mAb.IL-10geneexpressionpaternsdiferedfromstimulitostimuli,highlevelofgeneexpresionwasobservedintheHIVinfectiongroupstimulatedbyPHA,candidinandrIL-2(1000U),andlowlevelofexpresionstimulatedbyrIL-2(10U)andanti-CD3MAb.TNF-αgeneexpressioninHIVseropositivesubjectsstartedearlierandwithhigherlevel.IFN-γ,IL-10,IL-6andTNF-αgeneexpresionsinHIVseropositivesubjectsstimulatedbyIL-2were'dose-dependent',lowdose(10U)showedhighlevelsofIFN-γ,TNF-αandIL-6,lowIL-10,buthighdose(1000U)showedoppositeresultsascomparedwithHIVseronegativesubjects.IFN-γandIL-10geneex-pressionstimulatedbyrIL-2(10U),rIL-2(1000U),andanti-CD3mAbshowedreversedpatternsinbothHIVseropos-itiveandnegativesubjects,itindicatesthatthereisanendogenousregulationbetweenTh1andTh2cytokines.