Miller S D, Butler L D
J Immunol. 1983 Jul;131(1):77-85.
This report presents evidence for the role of antigen-specific helper T cells in augmenting the in vivo development of delayed-type hypersensitivity (DTH) responses to both hapten and protein antigens. The role of these helper T cells in the in vivo induction and regulation of DTH responses was investigated. Mice were primed subcutaneously with optimal numbers (3 X 10(7)) of either protein antigen- or TNP-modified syngeneic spleen cells. Primed spleen or lymph node cells, but not thymocytes or unprimed cells, were found to significantly augment the DTH response of syngeneic recipients injected subcutaneously with suboptimal numbers (1 to 2 X 10(6)) of antigen-modified syngeneic cells. Primed spleen or lymph node cells augmented both in vivo ear swelling reactions and in vitro antigen-induced T cell proliferative responses in recipient animals. The helper effect was found to be mediated by a population of radioresistant, Thy-1+, Lyt-1+2-, I-A+ cells, a phenotype identical to that of antigen-specific Tprlf cells found in primed lymph nodes. In contrast, effector TDH cells were found to be Thy-1+, Lyt-1+2-, I-A- cells. Splenic T cells from TNP-primed mice augmented TNP-specific DTH responses, but not DTH to irrelevant protein antigens, and vice versa. Helper T cell induction correlated with the presence of H-2 I-region determinants on the inducer cells, because antigen-modified spleen cells were the most efficient inducers, modified thymocytes were less efficient, and modified erythrocytes were ineffective. Mapping studies also indicated that I-region identity between the antigen-modified spleen cell immunogen and the Th donors was both necessary and sufficient for DTH Th cell induction. In addition, functional helper T cell activity could be both specifically tolerized and suppressed by the transfer or suppressor T cells raised by the i.v. injection of antigen-modified syngeneic cells.
本报告提供了证据，证明抗原特异性辅助性T细胞在增强对半抗原和蛋白质抗原的迟发型超敏反应（DTH）的体内发育中所起的作用。研究了这些辅助性T细胞在DTH反应的体内诱导和调节中的作用。用最佳数量（3×10⁷）的蛋白质抗原或TNP修饰的同基因脾细胞对小鼠进行皮下致敏。发现致敏的脾细胞或淋巴结细胞，而非胸腺细胞或未致敏细胞，能显著增强皮下注射次最佳数量（1至2×10⁶）抗原修饰同基因细胞的同基因受体的DTH反应。致敏的脾细胞或淋巴结细胞增强了受体动物体内的耳部肿胀反应和体外抗原诱导的T细胞增殖反应。发现辅助作用由一群抗辐射的、Thy-1⁺、Lyt-1⁺2⁻、I-A⁺细胞介导，其表型与在致敏淋巴结中发现的抗原特异性Tprlf细胞相同。相比之下，效应TDH细胞为Thy-1⁺、Lyt-1⁺2⁻、I-A⁻细胞。来自TNP致敏小鼠的脾T细胞增强了TNP特异性DTH反应，但对无关蛋白质抗原的DTH反应无增强作用，反之亦然。辅助性T细胞的诱导与诱导细胞上H-2 I区决定簇的存在相关，因为抗原修饰的脾细胞是最有效的诱导剂，修饰的胸腺细胞效率较低，而修饰的红细胞则无效。定位研究还表明，抗原修饰的脾细胞免疫原与Th供体之间的I区一致性对于DTH Th细胞的诱导既是必要的也是充分的。此外，功能性辅助性T细胞活性可通过静脉注射抗原修饰同基因细胞产生的转移或抑制性T细胞而被特异性耐受和抑制。
