Fairchild R L, Moorhead J W
J Immunol. 1986 Oct 1;137(7):2125-31.
Coculture of spleen cells from mice tolerized with 2,4-dinitrobenzenesulfonate (DNBS) and DNP-labeled spleen cells (DNP-SC) activates Lyt-2+ T suppressor cells (Ts) to synthesize and release a suppressor factor (SSF) into the supernatant, which suppresses the transfer of contact sensitivity to DNFB. The purpose of the present study was to examine in greater detail the signals required to activate DNBS-primed Ts to produce SSF. The supernatant from cultures of tolerant cells and glutaraldehyde-fixed DNP-SC did not have SSF. In contrast, the soluble cell lysate from these cultures did contain the suppressive activity. Pretreatment of glutaraldehyde-fixed DNP-SC with either anti-DNP or anti-class I, but not anti-class II MHC, antibodies blocked SSF synthesis. The addition of IL 1 to cultures of DNBS-tolerant cells and glutaraldehyde fixed DNP-SC restored the ability of the Ts to release the synthesized factor. These results indicate that Ts recognition of the hapten/class I MHC determinant stimulates the synthesis of SSF, and a costimulator is required to induce the release of the factor. The supernatants from cultures of either L3T4-depleted tolerant cells and DNP-SC or tolerant cells and anti-I-A antibody-treated DNP-SC had no SSF activity. The addition of a costimulator (IL 1) also restored the ability of the Ts to release the synthesized factor in cultures of L3T4-depleted tolerant cells and DNP-SC. These results suggest that an L3T4 cell in the DNBS-primed cell population interacts with I-A determinants on a cell in the DNP-stimulator population to initiate the generation of the mediator required for SSF release. This further suggests that the Ts is unable to induce the costimulator from the hapten-presenting cell during interaction with the DNP/class I MHC ligand. Therefore, the production of SSF is regulated not only by the presentation of the appropriate hapten/MHC determinant but also by the interactions of cells that function in generating the costimulator needed to induce release of the suppressor factor.
用2,4 - 二硝基苯磺酸盐（DNBS）耐受的小鼠脾细胞与二硝基苯酚（DNP）标记的脾细胞（DNP - SC）共培养，可激活Lyt - 2⁺ T抑制细胞（Ts），使其合成并释放一种抑制因子（SSF）到上清液中，该抑制因子可抑制对二硝基氟苯（DNFB）的接触敏感性转移。本研究的目的是更详细地研究激活经DNBS致敏的Ts产生SSF所需的信号。耐受细胞与戊二醛固定的DNP - SC共培养的上清液中没有SSF。相反，这些培养物的可溶性细胞裂解物确实含有抑制活性。用抗DNP或抗I类而非抗II类主要组织相容性复合体（MHC）抗体预处理戊二醛固定的DNP - SC可阻断SSF的合成。向经DNBS耐受的细胞与戊二醛固定的DNP - SC的培养物中添加白细胞介素1（IL 1）可恢复Ts释放合成因子的能力。这些结果表明，Ts对半抗原/I类MHC决定簇的识别刺激了SSF的合成，并且需要一种共刺激因子来诱导该因子的释放。来自L3T4耗尽的耐受细胞与DNP - SC或耐受细胞与抗I - A抗体处理的DNP - SC共培养的上清液没有SSF活性。添加共刺激因子（IL 1）也恢复了L3T4耗尽的耐受细胞与DNP - SC共培养物中Ts释放合成因子的能力。这些结果表明，DNBS致敏细胞群体中的L3T4细胞与DNP刺激细胞群体中的细胞上的I - A决定簇相互作用，以启动SSF释放所需介质的产生。这进一步表明，Ts在与DNP/I类MHC配体相互作用期间无法从抗原呈递细胞诱导共刺激因子。因此，SSF的产生不仅受适当的半抗原/MHC决定簇的呈递调节，还受在产生诱导抑制因子释放所需的共刺激因子中起作用的细胞间相互作用的调节。
