Manzotti Claire N, Liu Michael K P, Burke Fiona, Dussably Laure, Zheng Yong, Sansom David M
MRC Centre for Immune Regulation, University of Birmingham Medical School, UK.
Eur J Immunol. 2006 Jun;36(6):1413-22. doi: 10.1002/eji.200535170.
CD80 and CD86 have the capacity to either stimulate or inhibit T cell responses through their receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Blockade of CD80 and CD86 in autoimmune disease settings has revealed distinct outcomes, yet the differential functions of CD80 and CD86 are still unclear. We have studied the ability of individual ligands to stimulate primary responses in human CD4(+) T cells. Our data reveal both quantitative and qualitative differences between the ligands. Both CD80 and CD86 demonstrated the capacity to costimulate T cell proliferation. However, CD80 committed a greater number of T cells to divide with faster kinetics, consistent with it being a superior ligand for CD28. Once cell division had been initiated, all T cells undergoing cell division expressed CTLA-4, irrespective of whether CD80 or CD86 costimulation was used. However, only in the presence of CD80 was evidence of CTLA-4 engagement and inhibitory function observed. Finally, differences between CD80 and CD86 costimulation extended to the T cell phenotype, in particular the levels of CD40 ligand expression.
CD80和CD86能够通过其受体CD28和细胞毒性T淋巴细胞相关抗原4（CTLA-4）刺激或抑制T细胞反应。在自身免疫性疾病背景下阻断CD80和CD86已显示出不同的结果，但CD80和CD86的不同功能仍不清楚。我们研究了单个配体刺激人CD4(+) T细胞初始反应的能力。我们的数据揭示了配体之间的数量和质量差异。CD80和CD86都表现出共刺激T细胞增殖的能力。然而，CD80能使更多的T细胞以更快的动力学进行分裂，这表明它是CD28的一种更优配体。一旦细胞分裂开始，所有进行细胞分裂的T细胞都表达CTLA-4，无论使用的是CD80还是CD86共刺激。然而，只有在存在CD80的情况下，才能观察到CTLA-4参与和抑制功能的证据。最后，CD80和CD86共刺激之间的差异扩展到T细胞表型，特别是CD40配体表达水平。
