Abromson-Leeman S R, Jayaraman S, Dorf M E
Department of Pathology, Harvard Medical School, Boston, MA 02115.
J Immunol. 1990 Apr 1;144(7):2451-8.
Although Thy-1+ lymphocytes have been observed in lymphoid tissues of athymic mice, attempts to analyze these cells on the clonal level have previously yielded only populations of CD4-CD8+ cytolytic T cells. Furthermore, studies of responses of these cells to various mitogenic stimuli have demonstrated significant defects in the ability of these cells to proliferate in culture. We report here on the cloning and maintenance in long term culture of T cells from an athymic mouse stimulated in vitro with allogeneic spleen cells. Of 10 Thy-1+ clones, 7 CD4+CD8- and 3 CD4-CD8+ Ag-specific cells were obtained. Among the CD4+ T cells, we observed a variety of specificities, including an autoreactive I-Aq specific clone, a minor lymphocyte stimulating determinant (Mls)-reactive clone, and five allo-I-Ad-specific CD4+ clones; a class II-specific CD4-CD8+ clone was also obtained. In addition, we observed two Thy-1-CD3+ clones (one of which is also CD4+ and expresses V beta 8) which are constitutively responsive to the lymphokines IL-2 and IL-4. Of 11 clones tested, 7 produce IL-2 and/or IL-4 lymphokines after stimulation through the TCR, whereas 4 do not, requiring exogenous lymphokines for optimal responses to Ag. Of 10 clones tested for IL-2R expression, 3 had notably low levels, correlating with low proliferative responses to IL-2. The results reveal the spectrum of T cells available to a mouse which is congenitally athymic and describe the heterogeneity of immune defects expressed in such cells at the clonal level.
虽然在无胸腺小鼠的淋巴组织中已观察到Thy-1+淋巴细胞,但此前在克隆水平分析这些细胞的尝试仅得到了CD4-CD8+细胞毒性T细胞群体。此外,对这些细胞对各种促有丝分裂刺激反应的研究表明,这些细胞在培养中增殖的能力存在显著缺陷。我们在此报告从一只体外经同种异体脾细胞刺激的无胸腺小鼠中克隆并长期培养T细胞的情况。在10个Thy-1+克隆中,获得了7个CD4+CD8-和3个CD4-CD8+抗原特异性细胞。在CD4+T细胞中,我们观察到了多种特异性,包括一个自身反应性I-Aq特异性克隆、一个次要淋巴细胞刺激决定簇(Mls)反应性克隆以及5个同种异体I-Ad特异性CD4+克隆;还获得了一个II类特异性CD4-CD8+克隆。此外,我们观察到两个Thy-1-CD3+克隆(其中一个也是CD4+并表达Vβ8),它们对细胞因子IL-2和IL-4有组成性反应。在测试的11个克隆中,7个在通过TCR刺激后产生IL-2和/或IL-4细胞因子,而4个则不产生,需要外源性细胞因子才能对抗原产生最佳反应。在测试IL-2R表达的10个克隆中,3个的水平明显较低,这与对IL-2的低增殖反应相关。结果揭示了先天性无胸腺小鼠可用的T细胞谱,并描述了此类细胞在克隆水平表达的免疫缺陷的异质性。