De Carli M, Berthold S, Fickenscher H, Fleckenstein I M, D'Elios M M, Gao Q, Biagiotti R, Giudizi M G, Kalden J R, Fleckenstein B
Division of Clinical Immunology and Allergology, University of Florence, Italy.
J Immunol. 1993 Nov 1;151(9):5022-30.
T blasts of six established human CD4+ T cell clones with defined Ag specificity and cytokine secretion profile (3 Th1 and 3 Th2) were immortalized with Herpesvirus saimiri (HVS) and compared with their uninfected counterparts for their ability to proliferate, produce cytokines, and express cytolytic activity. HVS-transformed Th1 and Th2 clones neither substantially changed their original surface markers nor lose their ability to proliferate in response to their specific Ag but did acquire the ability to proliferate in response to contact signals delivered by SRBC or autologous APC alone. In addition, transformation by HVS substantially enhanced the lectin-dependent cytolytic activity of Th1 clones and enabled noncytolytic Th2 clones to exert cytolytic activity. HVS-transformed Th1 clones but not their uninfected counterparts spontaneously transcribed and secreted Th1-type cytokines (IL-2, IFN-gamma, and TNF-beta) and such a production was further enhanced by stimulation with either SRBC or PMA plus anti-CD3 mAb. HVS transformed but not uninfected Th2 clones constitutively expressed both IL-4 and IL-2 mRNA and secreted IFN-gamma. Stimulation with PMA plus anti-CD3 mAb induced uninfected Th2 clones to secrete high amounts of IL-4 and IL-5 but not Th1-type cytokines, whereas the same HVS-transformed Th2 showed minimal IL-4 and IL-5 secretion with concomitant high production of IL-2, IFN-gamma, and TNF-beta. Transformation by HVS also resulted in up-regulation of TNF-alpha and IL-3 production by both Th1 and Th2 clones. The ongoing proliferation of HVS-transformed clones was partially inhibited by either anti-IL-2 or anti-IL-3 antibodies and virtually abolished by the combined addition of the two anticytokine antibodies, suggesting that both IL-2 and IL-3 can function as autocrine growth factors for HVS-transformed Th1 and Th2 clones.
用赛米利疱疹病毒（HVS）使6个已建立的具有明确抗原特异性和细胞因子分泌谱的人CD4⁺T细胞克隆（3个Th1和3个Th2）的T淋巴母细胞永生化，并将其与未感染的对应细胞进行比较，观察它们在增殖、产生细胞因子和表达溶细胞活性方面的能力。HVS转化的Th1和Th2克隆既没有实质性改变其原始表面标志物，也没有丧失对其特异性抗原作出反应而增殖的能力，但确实获得了仅对SRBC或自体抗原呈递细胞传递的接触信号作出反应而增殖的能力。此外，HVS转化显著增强了Th1克隆的凝集素依赖性溶细胞活性，并使无溶细胞活性的Th2克隆能够发挥溶细胞活性。HVS转化的Th1克隆而非未感染的对应细胞自发转录并分泌Th1型细胞因子（IL-2、IFN-γ和TNF-β），用SRBC或PMA加抗CD3单克隆抗体刺激可进一步增强这种分泌。HVS转化而非未感染的Th2克隆组成性表达IL-4和IL-2 mRNA并分泌IFN-γ。用PMA加抗CD3单克隆抗体刺激可诱导未感染的Th2克隆分泌大量IL-4和IL-5，但不分泌Th1型细胞因子，而相同的HVS转化的Th2克隆IL-4和IL-5分泌极少，同时大量产生IL-2、IFN-γ和TNF-β。HVS转化还导致Th1和Th2克隆的TNF-α和IL-3产生上调。抗IL-2或抗IL-3抗体可部分抑制HVS转化克隆的持续增殖，而同时添加这两种抗细胞因子抗体则几乎完全消除增殖，这表明IL-2和IL-3均可作为HVS转化的Th1和Th2克隆的自分泌生长因子。
