Gajewski T F, Pinnas M, Wong T, Fitch F W
Department of Pathology, University of Chicago, IL 60637.
J Immunol. 1991 Mar 15;146(6):1750-8.
We recently have devised a method for the derivation of OVA-specific Th1 and Th2 clones from the same primed lymph node cell preparation. Using a panel of such cells, we have examined the ability of distinct APC populations to stimulate proliferation of Th1 and Th2 clones. Both subsets proliferated well in response to OVA in the presence of whole spleen cells. However, purified B cells stimulated optimal proliferation of Th2 clones, whereas adherent cells stimulated optimal proliferation of Th1 clones. The proliferative response of Th2 cells stimulated with spleen cells irradiated with 3300 rad was dramatically less than that observed in response to spleen cells treated with 1000 rad; Th1 clones responded similarly to spleen cells exposed to either irradiation dose. Differential activation of Th1 and Th2 clones did not correlate with MHC-restricting element, or susceptibility to inhibition by mAb directed against CD4 or LFA-1. Lymphokine production by each subset still occurred under conditions of suboptimal proliferation, suggesting that the appropriate Ag processing and presentation events had transpired. The same pattern of response was observed using a specific OVA peptide that does not require processing, suggesting that differential responsiveness of Th1 and Th2 clones to different APC populations is not a result of defective Ag processing. Neither rIL-1 nor rIL-6 restored optimal proliferation of either subset. Our results suggest that unique cofactors are necessary for the optimal proliferation of Th1 and Th2 clones, and that these cofactors are produced by specialized APC populations.
我们最近设计了一种方法，可从同一经致敏的淋巴结细胞制备物中获得卵清蛋白（OVA）特异性的Th1和Th2克隆。利用一组这样的细胞，我们检测了不同抗原呈递细胞（APC）群体刺激Th1和Th2克隆增殖的能力。在全脾细胞存在的情况下，两个亚群对OVA均有良好的增殖反应。然而，纯化的B细胞刺激Th2克隆的增殖最佳，而贴壁细胞刺激Th1克隆的增殖最佳。用3300拉德照射的脾细胞刺激Th2细胞的增殖反应明显低于用1000拉德处理的脾细胞所观察到的反应；Th1克隆对暴露于任一照射剂量的脾细胞反应相似。Th1和Th2克隆的差异激活与主要组织相容性复合体（MHC）限制性元件或针对CD4或淋巴细胞功能相关抗原-1（LFA-1）的单克隆抗体的抑制敏感性无关。在增殖次优的条件下，每个亚群仍会产生淋巴因子，这表明已经发生了适当的抗原加工和呈递事件。使用一种不需要加工的特异性OVA肽也观察到了相同的反应模式，这表明Th1和Th2克隆对不同APC群体的差异反应性不是抗原加工缺陷的结果。重组白细胞介素-1（rIL-1）和重组白细胞介素-6（rIL-6）均未恢复任一亚群的最佳增殖。我们的结果表明，独特的辅助因子对于Th1和Th2克隆的最佳增殖是必需的，并且这些辅助因子是由专门的APC群体产生的。
