Clerici M, Hakim F T, Venzon D J, Blatt S, Hendrix C W, Wynn T A, Shearer G M
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1993 Mar;91(3):759-65. doi: 10.1172/JCI116294.
Infection with HIV results in an incremental loss of T helper cell (TH) function, which can occur years before CD4 cell numbers are critically reduced and AIDS is diagnosed. All TH function is not affected, however, because B cell activation and hypergammaglobulinema are also characteristic of this period. Recently, in a murine model of AIDS an early loss in production of the CD4 cytokines IL-2 and IFN-gamma was correlated with an increase in the B cell stimulatory cytokines IL-4, IL-5, and IL-10. We therefore assessed the production of IL-4 generated by PBL from HIV-seropositive (HIV+) individuals who did not have AIDS, yet who exhibited different TH functional categories based on their IL-2 production profiles. We observed that the decreases in recall antigen-stimulated IL-2 production were accompanied by an increase in IL-4 production. The loss of recall antigen-stimulated responses in HIV+ individuals could be reversed in vitro by anti-IL-4 antibody. Our results suggest that the TH functions assessed by IL-4 production replace the normally dominant TH function of antigen-stimulated IL-2 production in the progression toward AIDS, and raise the possibility of cytokine cross-regulation in AIDS therapy.
感染艾滋病毒会导致辅助性T细胞（TH）功能逐渐丧失，这种情况可能在CD4细胞数量严重减少并被诊断为艾滋病之前数年就已出现。然而，并非所有TH功能都会受到影响，因为B细胞活化和高丙种球蛋白血症也是这一时期的特征。最近，在艾滋病小鼠模型中，CD4细胞因子白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）产生的早期减少与B细胞刺激细胞因子IL-4、IL-5和IL-10的增加相关。因此，我们评估了来自未患艾滋病但根据其IL-2产生情况表现出不同TH功能类别的艾滋病毒血清阳性（HIV+）个体的外周血淋巴细胞（PBL）产生IL-4的情况。我们观察到，回忆抗原刺激的IL-2产生减少的同时，IL-4产生增加。HIV+个体中回忆抗原刺激反应的丧失在体外可被抗IL-4抗体逆转。我们的结果表明，在向艾滋病进展过程中，通过IL-4产生评估的TH功能取代了抗原刺激的IL-2产生这一通常占主导的TH功能，并增加了艾滋病治疗中细胞因子交叉调节的可能性。
