Leclerc C, Schutze M P, Deriaud E, Przewlocki G
Laboratoire de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
J Immunol. 1990 Sep 1;145(5):1343-9.
Injection of mice with an immunogenic dose of carrier (keyhole limpet hemocyanin (KLH)) followed by immunization with hapten-carrier conjugate (TNP-KLH) selectively suppresses anti-hapten antibody response. In this study, the cellular basis of this epitopic suppression and also of the suppression induced by a high dose of carrier were analyzed by in vivo depletion of CD4+ or CD8+ T cell subsets by using mAb. The mAb treatments were performed either at the time of carrier priming or at the time of hapten-carrier immunization. The elimination of CD8+ T cells has not modified the anti-carrier antibody response, whether this treatment was performed at the time of KLH-priming or during TNP-KLH immunization. Moreover, the in vivo treatment with the anti-CD8 mAb did not modify the carrier-induced epitopic suppression induced either by a low immunogenic dose of KLH or by a high dose of this Ag. The elimination of CD4+ T cells at the time of KLH immunization has prevented the induction of a memory response to KLH, clearly establishing that CD4+ T cells are essential in memory B cell development to T-dependent Ag. Moreover, this treatment has totally abrogated the epitopic suppression induced either by low or high dosages of KLH. In contrast, the in vivo elimination of CD4+ T cells after carrier immunization did not abolish the secondary anti-carrier antibody response and did not prevent the expression of epitopic suppression. These data indicate that primed CD4+ T cells are required neither for memory B cell expression nor for the expression of suppression. Finally, once induced, the suppression can be evidenced after in vivo depletion of both primed CD4+ and CD8+ T cells. These data support the view that epitopic suppression is induced through the expansion of carrier-specific B cells and resulted from intramolecular antigenic competition between hapten and carrier epitopes.
给小鼠注射免疫原剂量的载体（钥孔戚血蓝蛋白（KLH）），随后用半抗原 - 载体偶联物（TNP - KLH）进行免疫，可选择性抑制抗半抗原抗体反应。在本研究中，通过使用单克隆抗体在体内清除CD4⁺或CD8⁺T细胞亚群，分析了这种表位抑制以及高剂量载体诱导的抑制的细胞基础。单克隆抗体处理在载体初次免疫时或半抗原 - 载体免疫时进行。无论这种处理是在KLH初次免疫时还是在TNP - KLH免疫期间进行，清除CD8⁺T细胞均未改变抗载体抗体反应。此外，用抗CD8单克隆抗体进行体内处理，并未改变由低免疫原剂量的KLH或高剂量该抗原诱导的载体诱导的表位抑制。在KLH免疫时清除CD4⁺T细胞可阻止对KLH记忆反应的诱导，明确证实CD4⁺T细胞在记忆B细胞发育为对T依赖性抗原的反应中至关重要。此外，这种处理完全消除了由低剂量或高剂量KLH诱导的表位抑制。相反，在载体免疫后体内清除CD4⁺T细胞并未消除二次抗载体抗体反应，也未阻止表位抑制的表达。这些数据表明，已致敏的CD4⁺T细胞对于记忆B细胞的表达或抑制的表达均非必需。最后，一旦诱导产生，在体内清除已致敏的CD4⁺和CD8⁺T细胞后仍可证明存在抑制作用。这些数据支持这样一种观点，即表位抑制是通过载体特异性B细胞的扩增诱导产生的，并且是由半抗原和载体表位之间的分子内抗原竞争导致的。
