Kitamura K, Kiyono H, Fujihashi K, Eldrige J H, Beagley K W, McGhee J R
Department of Microbiology, University of Alabama, Birmingham 35294.
J Immunol. 1988 Mar 1;140(5):1385-92.
In the present study, we have isolated and characterized the Lyt-1+, -2- T contrasuppressor (Tcs) cells from mice systemically primed with SRBC. Adoptive transfer of splenic Tcs cells from these mice abrogates oral tolerance and supports IgM and IgG anti-SRBC plaque-forming cell (PFC) responses; however, unlike the responses seen after transfer of Tcs cells derived from orally primed mice, low IgA responses were seen. Mice systemically primed with lower SRBC doses (0.01 to 1%) exhibited contrasuppression only within the L3T4- T cell subset, whereas mice primed with a high dose of SRBC (10%), harbored Lyt-1+, -2- Tcs cells in both the L3T4+ and L3T4- subsets. Both the L3T4- and L3T4+ Tcs cell subsets supported IgM and IgG responses when adoptively transferred to orally tolerized mice, and when added to tolerized spleen cell cultures. Splenic Tcs cells from systemically primed mice supported mainly IgG1 and IgG2b subclass anti-SRBC PFC responses, a pattern also seen with Tcs cells derived from orally primed mice. Both L3T4+ and L3T4- Tcs cells from systemically primed mice exhibited well established characteristics of contrasuppressor cells including binding to Vicia villosa lectin and expression of I-J. The splenic effector Tcs cells which support IgM, IgG1 and IgG2b anti-SRBC PFC responses are antigen-specific, since both L3T4- and L3T4+ Tcs cells from spleens of mice primed with 10% SRBC reverse tolerance to SRBC, but not to horse erythrocytes (HRBC). Further, both L3T4- and L3T4+ Tcs cells from HRBC-primed mice reverse tolerance to IgM and IgG anti-HRBC, but not to anti-SRBC responses. Isolation of T3-positive Lyt-1+, -2- and L3T4- Tcs cell subsets by flow cytometry followed by adoptive transfer, showed that effector Tcs cells express T3 and presumably contain an Ag-R (TCR-T3 complex). These studies show that systemic priming with heterologous RBC induces splenic Ag specific Tcs cells in a dose-dependent manner, which support IgM and IgG subclass responses, but not IgA responses.
在本研究中，我们从经绵羊红细胞（SRBC）全身致敏的小鼠中分离并鉴定了Lyt-1⁺、-2⁻ T抗抑制细胞（Tcs细胞）。将这些小鼠的脾Tcs细胞进行过继转移可消除口服耐受，并支持IgM和IgG抗SRBC斑块形成细胞（PFC）反应；然而，与经口服致敏小鼠来源的Tcs细胞转移后所见的反应不同，IgA反应较低。用较低SRBC剂量（0.01%至1%）全身致敏的小鼠仅在L3T4⁻ T细胞亚群内表现出抗抑制作用，而用高剂量SRBC（10%）致敏的小鼠在L3T4⁺和L3T4⁻亚群中均含有Lyt-1⁺、-2⁻ Tcs细胞。当将L3T4⁻和L3T4⁺ Tcs细胞亚群过继转移到口服耐受的小鼠中以及添加到耐受的脾细胞培养物中时，二者均支持IgM和IgG反应。经全身致敏小鼠的脾Tcs细胞主要支持IgG1和IgG2b亚类抗SRBC PFC反应，经口服致敏小鼠来源的Tcs细胞也呈现这种模式。经全身致敏小鼠的L3T4⁺和L3T4⁻ Tcs细胞均表现出抗抑制细胞的成熟特征，包括与野豌豆凝集素结合及I-J表达。支持IgM、IgG1和IgG2b抗SRBC PFC反应的脾效应Tcs细胞是抗原特异性的，因为用10% SRBC致敏小鼠脾脏中的L3T4⁻和L3T4⁺ Tcs细胞均可逆转对SRBC的耐受，但对马红细胞（HRBC）则无此作用。此外，经HRBC致敏小鼠的L3T4⁻和L3T4⁺ Tcs细胞均可逆转对IgM和IgG抗HRBC的耐受，但对抗SRBC反应则无此作用。通过流式细胞术分离T3阳性的Lyt-1⁺、-2⁻和L3T4⁻ Tcs细胞亚群，然后进行过继转移，结果显示效应Tcs细胞表达T3，推测其含有抗原受体（TCR-T3复合物）。这些研究表明，用异源红细胞进行全身致敏以剂量依赖方式诱导脾抗原特异性Tcs细胞，其支持IgM和IgG亚类反应，但不支持IgA反应。
