Babb J L, Kiyono H, Michalek S M, McGhee J R
J Immunol. 1981 Sep;127(3):1052-7.
The regulation of immune responses to gastrically administered TI antigens has been investigated, and the characterization of a regulatory cell population has been performed. Intragastric administration of TNP-haptenated homologous erythrocytes (TNP-MRBC) induced splenic IgM anti-TNP PFC responses in LPS nonresponsive C3H/HeJ mice that were higher than those in LPS-responsive C3H/HeN mice and similar to those noted in athymic (nu/nu) C3H/HeN animals. The simultaneous intragastric administration of LPS with TNP-MRBC augmented immune responses in a manner similar to that previously reported for parenterally administered LPS and antigen. Further, LPS-induced augmentation of TNP-MRBC responses was greater in athymic mice. These findings were substantiated using in vitro spleen cultures. Intragastric challenge with a 2nd TI antigen, TNP-LPS, induced approximately 8-fold higher splenic anti-TNP PFC responses in athymic C3H/HeN mice compared with those in euthymic littermates. By admixture of B and T cell populations, it was demonstrated that the host responsiveness to TNP-LPS was negatively regulated by suppressor cells. Suppressive activity resided in a Thy 1.2-bearing, irradiation-resistant, nylon wool-nonadherent cell population. These cells could be demonstrated in spleen and Peyer's patches from young or old LPS-responsive C3H/HeN mice, but not in tissues from LPS nonresponsive C3H/HeJ mice. The specificity of the regulator cells was not limited to TNP-LPS responses, since immune responsiveness to another TI antigen, TNP-dextran, was also under the control of this cell population. These studies confirm the TI nature of TNP-MRBC and indicate that immune responses to gastrically administered antigens such as TNP-LPS, TNP-dextran, and possibly TNP-MRBC are negatively regulated by a suppressor T cell population. A role for endogenous LPS in the generation of regulator cells and the effect of these cells on host responses to gut-derived antigens is discussed.
对经胃给予的TI抗原的免疫反应调节已被研究，并对调节细胞群体进行了特性鉴定。在LPS无反应性的C3H/HeJ小鼠中，经胃给予TNP-半抗原化的同源红细胞（TNP-MRBC）诱导的脾IgM抗-TNP PFC反应高于LPS反应性的C3H/HeN小鼠，且与无胸腺（nu/nu）C3H/HeN动物中观察到的反应相似。同时经胃给予LPS和TNP-MRBC以类似于先前报道的经肠外给予LPS和抗原的方式增强免疫反应。此外，LPS诱导的TNP-MRBC反应增强在无胸腺小鼠中更大。这些发现通过体外脾培养得到证实。用第二种TI抗原TNP-LPS经胃攻击，与有胸腺的同窝小鼠相比，无胸腺的C3H/HeN小鼠的脾抗-TNP PFC反应诱导高出约8倍。通过混合B细胞和T细胞群体，证明宿主对TNP-LPS的反应性受到抑制细胞的负调节。抑制活性存在于表达Thy 1.2、抗辐射、不黏附尼龙毛的细胞群体中。这些细胞可在年轻或年老的LPS反应性C3H/HeN小鼠的脾脏和派尔集合淋巴结中检测到，但在LPS无反应性的C3H/HeJ小鼠的组织中未检测到。调节细胞的特异性不限于TNP-LPS反应，因为对另一种TI抗原TNP-葡聚糖的免疫反应性也受该细胞群体的控制。这些研究证实了TNP-MRBC的TI性质，并表明对经胃给予的抗原如TNP-LPS、TNP-葡聚糖以及可能的TNP-MRBC的免疫反应受到抑制性T细胞群体的负调节。讨论了内源性LPS在调节细胞生成中的作用以及这些细胞对宿主对肠道来源抗原反应的影响。
