Nonoyama S, Penix L A, Edwards C P, Lewis D B, Ito S, Aruffo A, Wilson C B, Ochs H D
Department of Pediatrics, University of Washington, Seattle 98195.
J Clin Invest. 1995 Jan;95(1):66-75. doi: 10.1172/JCI117677.
CD40 and CD40 ligand (gp39) mediate contact-dependent T-B cell interaction. We determined the expression of CD40 ligand by activated neonatal T cells and the response of neonatal B cells when activated through CD40. Although expression of CD40 ligand peaked simultaneously in both activated adult and neonatal cells, neonatal T cells expressed significantly less CD40 ligand surface protein and mRNA than adult T cells. Activated thymocytes also expressed far less CD40 ligand than adult T cells. Consistent with these results, activated neonatal T cells exhibited less helper function than activated adult T cells. Neonatal T cells primed and restimulated in vitro expressed CD40 ligand in amounts comparable with adult T cells and provided B cell help more effectively. This suggests that the poor expression of CD40 ligand reflects antigenic naiveté rather than an intrinsic defect of neonatal T cells. Neonatal B cells cultured with soluble CD40 ligand (sgp39) and IL-10 produced IgM in amounts comparable with adult cells, but much less IgG and IgA. Nevertheless, neonatal B cells were capable of proliferation and class switching, since sgp39 and IL-4 induced proliferation and IgE production comparable to adult B cells and production of modest amounts of IgG. Together, these results indicate that diminished CD40 ligand expression, along with decreased production of lymphokines, may be responsible, at least in part, for the transient immunodeficiency observed in human neonates.
CD40与CD40配体(gp39)介导接触依赖性T细胞与B细胞的相互作用。我们测定了活化的新生T细胞中CD40配体的表达情况,以及新生B细胞通过CD40活化后的反应。尽管活化的成年细胞和新生细胞中CD40配体的表达峰值同时出现,但新生T细胞表达的CD40配体表面蛋白和mRNA明显少于成年T细胞。活化的胸腺细胞表达的CD40配体也远少于成年T细胞。与这些结果一致,活化的新生T细胞表现出的辅助功能比活化的成年T细胞少。在体外进行初次致敏和再次刺激的新生T细胞表达的CD40配体数量与成年T细胞相当,并且能更有效地为B细胞提供辅助。这表明CD40配体表达不佳反映的是抗原幼稚性,而非新生T细胞的内在缺陷。用可溶性CD40配体(sgp39)和白细胞介素-10培养的新生B细胞产生的IgM数量与成年细胞相当,但产生的IgG和IgA要少得多。然而,新生B细胞能够增殖和类别转换,因为sgp39和白细胞介素-4诱导的增殖和IgE产生与成年B细胞相当,并且能产生少量的IgG。总之,这些结果表明,CD40配体表达减少以及淋巴因子产生减少可能至少部分导致了人类新生儿中观察到的短暂免疫缺陷。