Hardy G A D, Imami N, Sullivan A K, Pires A, Burton C T, Nelson M R, Gazzard B G, Gotch F M
Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, London.
Clin Exp Immunol. 2003 Oct;134(1):98-106. doi: 10.1046/j.1365-2249.2003.02256.x.
Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.
功能性CD4(+) T细胞对体外刺激反应性的重建与持续高效抗逆转录病毒治疗(HAART)相关。36名未接受过抗逆转录病毒治疗的患者接受了为期16周的HAART治疗。在每个时间点评估抗原特异性、丝裂原和白细胞介素(IL)-2诱导的淋巴细胞增殖反应以及特异性IL-2和IL-4的产生,同时对HIV-1 RNA载量和淋巴细胞群体进行定量分析。回忆反应的重建主要限于单纯疱疹病毒和念珠菌等持续性抗原,而非HIV-1或新抗原。回忆抗原、丝裂原和IL-2诱导的新反应与体外IL-2的产生有关,但与IL-4无关。对低浓度与高浓度IL-2刺激的差异反应性呈逐步增加,提示IL-2受体表达正常化且功能改善。体外增殖反应的这些增加可能反映了由与持续长期存在的生物体相关的持续抗原刺激驱动的短期效应克隆。在这种情况下,对HIV-1抗原无反应提示存在持续的HIV-1特异性克隆性T细胞无反应性。