Walker P R, Fellowes R, Hecht E M, Lehner T
Department of Immunology, United Medical School Guy's Hospital, London, England.
J Immunol. 1991 Nov 15;147(10):3370-80.
T cell clones were generated from the peripheral blood of rhesus monkeys that had been immunized with a soluble Mr 185,000 Ag (SAI/II) derived from Streptococcus mutans. The clones were CD3+ CD8+ CD4- alpha beta TCR+ and were specifically stimulated to proliferate by SAI/II. The proliferative responses of the cloned cells were class I restricted, as demonstrated by reconstitution of the cloned T cells with APC matched at various MHC class I and II loci, as well as by inhibition with anti-class I and not anti-class II mAb. The function of the CD8+ cloned cells was examined in vitro for their effect on antibody synthesis by Ag-stimulated CD4+ cells and B cells from immunized animals. Indeed, four of the five clones suppressed SAI/II-specific IgG antibody synthesis when activated with SAI/II and the appropriate MHC-matched APC. Although activation of the suppressor clones was Ag specific, the effector function of the suppression of antibody synthesis was Ag nonspecific. The latter was probably mediated by lymphokines and, indeed, the culture supernatant generated by stimulating the cloned CD8+ cells with anti-CD3 mAb suppressed both the specific and nonspecific antibody synthesis. Cytotoxicity studies showed that all five CD8+ clones showed a low level of lectin-dependent cytotoxicity. However, because four of the five clones expressed significant suppression of antibody synthesis, the suppressor activity was unlikely to be a function of the weak cytotoxicity. The results suggest that immunization of rhesus monkeys with a soluble streptococcal Ag induced CD8+ alpha beta TCR+ T cell clones that show SAI/II-specific, MHC class I-restricted proliferative responses and nonspecific down-regulatory function of in vitro antibody synthesis.
T细胞克隆是从恒河猴外周血中产生的，这些恒河猴已用源自变形链球菌的可溶性分子量为185,000的抗原（SAI/II）进行免疫。这些克隆为CD3 + CD8 + CD4 - αβTCR +，并被SAI/II特异性刺激增殖。通过用在各种MHC I类和II类基因座匹配的APC重建克隆的T细胞，以及用抗I类而非抗II类单克隆抗体抑制，证明克隆细胞的增殖反应受I类限制。在体外检查CD8 +克隆细胞对来自免疫动物的抗原刺激的CD4 +细胞和B细胞抗体合成的影响。实际上，五个克隆中的四个在用SAI/II和适当的MHC匹配的APC激活时抑制了SAI/II特异性IgG抗体合成。虽然抑制性克隆的激活是抗原特异性的，但抗体合成抑制的效应功能是非抗原特异性的。后者可能由淋巴因子介导，事实上，用抗CD3单克隆抗体刺激克隆的CD8 +细胞产生的培养上清液抑制了特异性和非特异性抗体合成。细胞毒性研究表明，所有五个CD8 +克隆均表现出低水平的凝集素依赖性细胞毒性。然而，由于五个克隆中的四个表现出对抗体合成的显著抑制，抑制活性不太可能是弱细胞毒性的功能。结果表明，用可溶性链球菌抗原免疫恒河猴可诱导CD8 +αβTCR + T细胞克隆，这些克隆表现出SAI/II特异性、MHC I类限制的增殖反应和体外抗体合成的非特异性下调功能。
