Costimulation through CD28 enhances T cell-dependent B cell activation via CD40-CD40L interaction.
Costimulation through CD28 enhances T cell-dependent B cell activation via CD40-CD40L interaction.
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DOI：
10.4049/jimmunol.152.12.5643
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发表时间：
1994-06
影响因子：
4.4
通讯作者：
S. Klaus;L. Pinchuk;H. Ochs;C. Law;W. Fanslow;R. Armitage;E. Clark
中科院分区：
文献类型：
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作者：
S. Klaus;L. Pinchuk;H. Ochs;C. Law;W. Fanslow;R. Armitage;E. Clark
当抗 CD3 激活的 T 细胞与 CD28 受体（抗 CD28）单克隆抗体共刺激时，分析了 T 细胞辅助功能的变化。如果抗 CD3 刺激的 T 细胞与抗 CD28 同时激活，则 T 细胞依赖性 B 细胞生长和分化会持续增强。尽管抗 CD28 增强了 IL-2 和 IL-4 的产生，但它并不能仅通过增加可溶性淋巴因子的产生来增加 B 细胞反应。抗 CD28 共刺激可诱导 T 细胞 CD40 配体 (CD40L) 增加，已知该配体可促进 B 细胞增殖和 Ig 分泌。由于抗 CD28 促进 T 细胞辅助功能和 CD40L 的表达，因此我们检查了 T 细胞依赖性 B 细胞反应期间 CD40L 的依赖性。尽管可溶性 CD40 融合蛋白仅部分抑制 T 细胞依赖性 B 细胞激活，但我们发现启动 B 细胞反应时对 CD40L 表达有严格要求。 TCR 交联后，CD40L 表达和 T 细胞帮助均被环孢菌素 A 阻断，并且与 T 细胞增殖不同，两者在 CD28 共刺激期间仍保持环孢菌素 A 敏感性。此外，抗CD28不能弥补缺乏功能性CD40L的高IgM综合征患者的T细胞辅助缺陷。因此，抗 CD28 诱导的 T 细胞帮助是通过 CD40L 依赖性过程传递的。 B 细胞上交联 CD40 促进 CD28 的 B7/BB-1 配体表达这一事实表明，T 和 B 相互作用可能具有相互放大机制。
Changes in T cell helper function were analyzed when anti-CD3-activated T cells were costimulated with mAbs to the CD28 receptor (anti-CD28). T cell-dependent B cell growth and differentiation were consistently augmented if anti-CD3 stimulated-T cells were simultaneously activated with anti-CD28. Although anti-CD28 enhanced IL-2 and IL-4 production, it did not increase B cell responses solely by augmenting production of soluble lymphokines. Anti-CD28 costimulation induced increases on T cells of CD40 ligand (CD40L), known to promote B cell proliferation and Ig secretion. Because anti-CD28 promoted T cell helper functions and expression of CD40L, we examined the dependence for CD40L during T cell-dependent B cell responses. Although soluble CD40 fusion proteins only partially inhibited T cell-dependent B cell activation, we found a strict requirement for CD40L expression at initiating B cell responses. Both CD40L expression and T cell help were blocked by cyclosporin A after TCR cross-linking, and, unlike T cell proliferation, both remained cyclosporin A sensitive during CD28 costimulation. In addition, anti-CD28 could not compensate for the T cell helper deficiency of hyper IgM syndrome patients who lack functional CD40L. Thus, anti-CD28-induced T cell help is delivered via a CD40L-dependent process. The fact that cross-linking CD40 on B cells promotes expression of the B7/BB-1 ligand for CD28 suggest T and B interactions may have a reciprocal amplification mechanism.