Transplantation. 2010 May 27;89(10):1208-17. doi: 10.1097/TP.0b013e3181df53dc.
Blockade of costimulatory molecules is a potent method of inducing long-term graft survival. We have previously addressed the issue of donor-reactive T-cell precursor frequency on relative costimulation dependence and found that the presence of a high precursor frequency of donor-reactive CD8 T cells resulted in costimulation blockade-resistant graft rejection, whereas the presence of a low-frequency donor-reactive population did not. To address the mechanisms by which high-frequency T cells obviated the requirement for costimulation, we asked whether a low-frequency population responding concomitantly with a high-frequency response also demonstrated costimulation independence.
A model system was established in which B6 mice containing a low frequency of anti-membrane bound chicken ovalbumin (mOVA) responders and a high frequency of anti-BALB/c responders received a skin graft from B6.mOVAxBALB/c F1 donors in the presence or absence of cytotoxic T-lymphocyte antigen-4 Ig/anti-CD154 costimulatory blockade.
The results revealed that in the presence of costimulation blockade, high-frequency anti-BALB/c T cells augmented the effector activity of low-frequency anti-mOVA T cells, but it did not enhance the accumulation of anti-mOVA T cells capable of mediating graft rejection.
These results demonstrate that both antigen-specific and antigen-independent factors contribute to the relative costimulation independence of high-frequency T-cell responses.
阻断共刺激分子是诱导长期移植物存活的有效方法。我们之前已经研究了供体反应性 T 细胞前体频率对相对共刺激依赖性的问题，发现供体反应性 CD8 T 细胞的高前体频率导致共刺激阻断抵抗的移植物排斥，而低频率供体反应性群体则不会。为了解释高频 T 细胞规避共刺激需求的机制，我们想知道同时具有高频反应的低频群体是否也表现出共刺激独立性。
建立了一个模型系统，其中 B6 小鼠含有低频率的抗膜结合鸡卵清蛋白（mOVA）反应者和高频率的抗 BALB/c 反应者，在存在或不存在细胞毒性 T 淋巴细胞抗原-4 Ig/抗-CD154 共刺激阻断的情况下，从 B6.mOVAxBALB/c F1 供体接受皮肤移植物。
结果表明，在共刺激阻断存在的情况下，高频抗 BALB/c T 细胞增强了低频抗 mOVA T 细胞的效应活性，但并未增强能够介导移植物排斥的抗 mOVA T 细胞的积累。
这些结果表明，抗原特异性和非抗原性因素都有助于高频 T 细胞反应的相对共刺激独立性。
