Van Neerven R J, Van de Pol M M, Van der Zee J S, Stiekema F E, De Boer M, Kapsenberg M L
Laboratory of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands.
Clin Exp Allergy. 1998 Jul;28(7):808-16. doi: 10.1046/j.1365-2222.1998.00306.x.
Allergen-specific T lymphocytes biased to the production of type 2 cytokines play an important role in the pathophysiology of atopic disease. It is not known whether optimal activation of these T cells requires costimulation via interaction of B7 (CD86/CD80) with CD28.
Peripheral blood mononuclear cells (PBMC), isolated from 10 house dust mite Dermatophagoides pteronyssinus (Der p)-allergic asthma patients and 10 non-allergic control individuals, were stimulated with house dust mite (Der p) and the control antigens Candida albicans (CA) and tetanus toxoid (TT). The role of costimulation in activation for proliferation and cytokine mRNA production of peripheral blood T cells was studied by blocking CD28, CTLA-4, and their ligands CD80 (B7-1) and CD86 (B7-2).
The proliferation and the production of type 1 and 2 cytokine mRNA by T cells in response to Der p as well as the control antigens TT and CA was inhibited by simultaneously masking CD80 and CD86 using CTLA4-Ig, a soluble form of CTLA-4. Notably, Der p-specific proliferation of T cells from Der p-allergic asthma patients and non-allergic controls were inhibited equally well. Additional experiments with MoAbs revealed that activation of these T cells was optimally inhibited by blocking the interaction of CD28 with CD86.
In vitro responses of allergen- and antigen-specific T cells of allergic patients and non-allergic control persons are equally dependent on costimulation via the CD28-CD86 pathway, suggesting that inhibition of this pathway may prevent complete activation of allergen-specific T cells in allergic individuals in vivo.
偏向于产生2型细胞因子的变应原特异性T淋巴细胞在特应性疾病的病理生理学中起重要作用。目前尚不清楚这些T细胞的最佳激活是否需要通过B7（CD86/CD80）与CD28的相互作用进行共刺激。
从10名屋尘螨（粉尘螨）过敏哮喘患者和10名非过敏对照个体中分离出外周血单个核细胞（PBMC），用屋尘螨（粉尘螨）以及对照抗原白色念珠菌（CA）和破伤风类毒素（TT）进行刺激。通过阻断CD28、CTLA-4及其配体CD80（B7-1）和CD86（B7-2），研究共刺激在外周血T细胞激活以进行增殖和细胞因子mRNA产生中的作用。
使用CTLA4-Ig（一种可溶性形式的CTLA-4）同时掩盖CD80和CD86，可抑制T细胞对粉尘螨以及对照抗原TT和CA的增殖以及1型和2型细胞因子mRNA的产生。值得注意的是，来自粉尘螨过敏哮喘患者和非过敏对照的T细胞的粉尘螨特异性增殖受到同等程度的抑制。用单克隆抗体进行的额外实验表明，通过阻断CD28与CD86的相互作用可最佳地抑制这些T细胞的激活。
过敏患者和非过敏对照个体的变应原和抗原特异性T细胞的体外反应同样依赖于通过CD28-CD86途径的共刺激，这表明抑制该途径可能会在体内阻止过敏个体中变应原特异性T细胞的完全激活。
