Krinzman S J, De Sanctis G T, Cernadas M, Mark D, Wang Y, Listman J, Kobzik L, Donovan C, Nassr K, Katona I, Christiani D C, Perkins D L, Finn P W
Pulmonary Division, Massachusetts General Hospital, Boston, USA.
J Clin Invest. 1996 Dec 15;98(12):2693-9. doi: 10.1172/JCI119093.
Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma.
初始T细胞的激活至少需要两个信号。除了T细胞抗原受体与抗原呈递细胞上表达的抗原/MHC之间已得到充分表征的相互作用外，T细胞激活还需要第二组信号的共刺激。最具特征的共刺激受体是CD28，它与抗原呈递细胞上表达的B7配体家族结合。在哮喘中，虽然活化的T细胞在气道炎症的起始和维持中起作用，但T细胞共刺激在支气管高反应性中的重要性尚未得到表征。因此，我们测试了这样一个假设，即抑制CD28:B7共刺激途径将消除气道高反应性。我们的结果表明，用CTLA4-Ig阻断共刺激（一种已知通过阻断CD28:B7相互作用来防止共刺激的融合蛋白）可抑制这种过敏性哮喘小鼠模型中的气道高反应性、炎性浸润、胸腔淋巴细胞扩增以及胸腔T细胞的过敏原特异性反应性。
