Araneo B A, Dowell T, Bertelsen K
Department of Pathology, University of Utah, Salt Lake City 84132.
Eur J Immunol. 1988 Apr;18(4):585-92. doi: 10.1002/eji.1830180415.
The present study tests whether the specific inhibition of helper T (Th) cell (and T hybridomas) by suppressor T (Ts) cells is a phenotypic trait of Th cells correlating with their acquired specificity for antigen/major histocompatibility complex or a genotypic trait not related to selection of the T cell repertoire for antigen. To do this we took advantage of the fact that H-2d parental strains of mice commonly restrict recognition of chicken egg-white lysozyme to the L3 peptide (a.a. 105-129) and H-2b parental mice to the L2 peptide (a.a. 13-105). F1 hybrids of these strains display two subsets of lysozyme-reactive T cells, one for each parental phenotype. Using (B10 X B10.D2)F1 mice reconstituted with B10.D2 bone marrow, we were able to develop genetic H-2d T cell clones that could express an atypical specificity, that is L2/I-Ab. Clones of this type, like genetic H-2b, are also sensitive to the inhibiting effects of HEL-activated Ts cells. To overcome some of the drawbacks of using heterogeneous populations of T, B and accessory cells in our assays, we constructed T hybridomas from HEL-immune, chimeric lymph node T cell blasts which respond to a unique antigen/major histocompatibility complex with production of the lymphokine interleukin 2. Our results indicate that all HEL/I-Ab-specific T cells (helper and hybridomas) are inhibited by suppression regardless of the T cell's haplotype at the H-2 locus: H-2b (B10), H-2d (D2) or H-2b,d (BDF1). Furthermore, there is a strict correlation between the antigen and I-A specificity: I-Ab-restricted T cells recognize non-L3 determinants even though some are derived from H-2d mice.
本研究旨在测试抑制性T细胞（Ts细胞）对辅助性T细胞（Th细胞）（及T杂交瘤）的特异性抑制作用，是与Th细胞针对抗原/主要组织相容性复合体的获得性特异性相关的表型特征，还是与针对抗原的T细胞库选择无关的基因型特征。为此，我们利用了这样一个事实，即H-2d系亲代小鼠通常将鸡卵清溶菌酶的识别限制在L3肽（氨基酸105 - 129），而H-2b系亲代小鼠则限制在L2肽（氨基酸13 - 105）。这些品系的F1杂种表现出两个溶菌酶反应性T细胞亚群，每种亲代表型各有一个。用B10.D2骨髓重建的（B10×B10.D2）F1小鼠，我们能够培养出可表达非典型特异性即L2/I-Ab的遗传性H-2d T细胞克隆。这种类型的克隆，与遗传性H-2b克隆一样，也对HEL激活的Ts细胞的抑制作用敏感。为克服在我们的实验中使用T、B和辅助细胞异质群体的一些缺点，我们从对独特抗原/主要组织相容性复合体有反应并产生淋巴因子白细胞介素2的HEL免疫嵌合淋巴结T细胞母细胞构建了T杂交瘤。我们的结果表明，所有HEL/I-Ab特异性T细胞（辅助性T细胞和杂交瘤）均受到抑制，而不论T细胞在H-2位点的单倍型如何：H-2b（B10）、H-2d（D2）或H-2b,d（BDF1）。此外，抗原与I-A特异性之间存在严格的相关性：I-Ab限制的T细胞识别非L3决定簇，即使有些细胞源自H-2d小鼠。
