Padula S J, Pollard M K, Lingenheld E G, Clark R B
J Clin Invest. 1985 Mar;75(3):788-97. doi: 10.1172/JCI111774.
The in vitro growth of T cells obtained from localized anatomic sites of pathology may offer a new approach to the investigation of certain human autoimmune diseases. However, if interleukin-2-dependent T cell cloning is to be useful in helping to elucidate putative pathogenetic antigens in these diseases, the expansion of the small number of T cells obtainable from localized anatomic sites of pathology will often have to be accomplished in the absence of these, as yet undetermined, antigens. At present, it is a generally held belief that antigen-responsive, interleukin-2-dependent T cell lines and clones will lose antigen responsiveness if propagated in the absence of specific antigen. Thus, the use of T cell cloning might be viewed as being of limited usefulness in the investigation of certain human autoimmune diseases. In this report we demonstrate that, when propagated in the absence of antigen, human tetanus toxoid-specific, interleukin-2-dependent T cell lines will indeed lose antigen reactivity. However, if propagated in the absence of antigen but in the presence of antigen-presenting cells, the tetanus toxoid reactivity of a subset of such lines can be maintained. Moreover, the propagation with OKT3 antibody, in addition to antigen-presenting cells, may be even more effective in maintaining antigen reactivity. These results may suggest a new approach to the use of T cell cloning technology in the investigation of certain autoimmune diseases.
从局部病理解剖部位获取的T细胞的体外生长可能为某些人类自身免疫性疾病的研究提供一种新方法。然而,如果白细胞介素-2依赖的T细胞克隆要有助于阐明这些疾病中假定的致病抗原,那么从局部病理解剖部位获取的少量T细胞的扩增通常必须在没有这些尚未确定的抗原的情况下完成。目前,人们普遍认为,抗原反应性、白细胞介素-2依赖的T细胞系和克隆如果在没有特异性抗原的情况下繁殖,将失去抗原反应性。因此,在某些人类自身免疫性疾病的研究中,T细胞克隆的用途可能被认为是有限的。在本报告中,我们证明,当在没有抗原的情况下繁殖时,人类破伤风类毒素特异性、白细胞介素-2依赖的T细胞系确实会失去抗原反应性。然而,如果在没有抗原但有抗原呈递细胞的情况下繁殖,这类细胞系的一个亚群的破伤风类毒素反应性可以维持。此外,除了抗原呈递细胞外,用OKT3抗体进行繁殖在维持抗原反应性方面可能更有效。这些结果可能为在某些自身免疫性疾病的研究中使用T细胞克隆技术提供一种新方法。