Emory Transplant Center and Department of Surgery, Emory University, Atlanta, GA 30079, United States.
Transpl Immunol. 2011 Jan 15;24(2):94-9. doi: 10.1016/j.trim.2010.11.002. Epub 2010 Nov 10.
Blockade of T cell costimulatory molecules represents a promising new method of attenuating donor-reactive T cell responses to promote graft survival following transplantation. However, recent studies in murine models have shown the presence of an initial high frequency of naïve donor-reactive T cells may render this strategy ineffective.
In this report, we examined the phenotypic changes associated with CD28 blockade on T cells stimulated at increasing precursor frequencies in vitro.
We found that treatment with the CD28 blocker CTLA-4 Ig resulted in downregulation of the alpha chain of the IL-2 receptor (CD25) in a division-dependent manner. Significantly, blockade of the CD28 pathway was more effective in down-regulating CD25 when the donor-reactive T cell population was present at low as compared to high precursor frequency.
These results imply that treatment with CD28 blockers and anti-CD25 mAbs may cooperate in promoting graft survival under conditions of low MHC matching where the donor-reactive T cell precursor frequency is high.
阻断 T 细胞共刺激分子是一种有前途的新方法，可以减弱供体反应性 T 细胞对移植后移植物存活的反应。然而，最近在鼠模型中的研究表明，初始高频率的幼稚供体反应性 T 细胞的存在可能使这种策略无效。
在本报告中，我们研究了在体外以递增的前体频率刺激 T 细胞时与 CD28 阻断相关的表型变化。
我们发现，用 CD28 阻断剂 CTLA-4 Ig 处理会导致 IL-2 受体（CD25）的α链以分裂依赖性方式下调。重要的是，当供体反应性 T 细胞群体存在于低而非高前体频率时，阻断 CD28 途径在下调 CD25 方面更有效。
这些结果表明，在 MHC 匹配程度低且供体反应性 T 细胞前体频率高的情况下，用 CD28 阻断剂和抗 CD25 mAb 治疗可能会协同促进移植物存活。
