In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39.
In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39.
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DOI：
10.1084/jem.178.5.1567
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发表时间：
1993-11-01
期刊：
影响因子：
--
通讯作者：
Noelle RJ
中科院分区：
文献类型：
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作者：
Foy TM;Shepherd DM;Durie FH;Aruffo A;Ledbetter JA;Noelle RJ
CD 40的配体最近被鉴定为39-kd蛋白，gp 39，表达于活化的CD 4 + T辅助细胞（Th）的表面上。在体外，可溶性CD 40和抗gp 39已经显示出阻断Th活化B细胞的能力，表明gp 39-CD 40相互作用对于T细胞依赖性B细胞活化是重要的。在这里，它表明，在体内施用抗gp 39显着降低了主要和次要的体液免疫反应，红细胞和可溶性蛋白抗原，而不改变对T-非依赖性II型抗原，三硝基苯基-Ficoll的反应。用抗gp 39治疗小鼠4 d可抑制抗绵羊红细胞（SRBC）反应至少3周，并抑制所有免疫球蛋白同种型在对蛋白抗原钥孔血蓝蛋白的次级反应中的表达。为了检查抗gp 39对Th功能的直接作用，过继转移来自抗gp 39处理的小鼠的SRBC免疫Th细胞，并且显示其完全能够提供帮助。这些结果表明，抗gp 39治疗不会导致Th缺失或无反应性。抗gp 39可能通过阻断gp 39-CD 40相互作用而介导其对体液免疫的深刻免疫抑制作用。此外，这些研究确立了gp 39-CD 40作为用于靶向治疗性抗体以控制胸腺依赖性体液应答的重要受体-配体对。
The ligand for CD40 has been recently identified as a 39-kd protein, gp39, expressed on the surface of activated CD4+ T helper cells (Th). In vitro, soluble CD40 and anti-gp39 have been shown to block the ability of Th to activate B cells, suggesting that gp39-CD40 interactions are important to T cell-dependent B cell activation. Here it is shown that in vivo administration of anti-gp39 dramatically reduced both primary and secondary humoral immune responses to erythrocytes and soluble protein antigens without altering responses to the T-independent type II antigen, trinitrophenyl-Ficoll. Treatment of mice for 4 d with anti-gp39 inhibited the anti-sheep red blood cell (SRBC) response for at least 3 wk and inhibited the expression of all immunoglobulin isotypes in secondary responses to the protein antigen, keyhole limpet hemocyanin. To examine the direct effect of anti-gp39 on Th function, SRBC-immune Th cells from anti-gp39-treated mice were adoptively transferred and shown to be fully capable of providing help. These results suggest that anti-gp39 treatment does not cause Th deletion or anergy. Anti-gp39 may mediate its profound immunosuppressive effects on humoral immunity by blocking gp39-CD40 interactions. Moreover, these studies establish gp39-CD40 as an important receptor-ligand pair for the targeting of therapeutic antibodies to control thymus-dependent humoral responses.