Morrison W J, Kennedy N J, Offner H, Vandenbark A A
Department of Pharmacology, Oregon Health Sciences University, Portland 97201, USA.
Int J Immunopharmacol. 1995 Dec;17(12):1017-25. doi: 10.1016/0192-0561(95)00076-3.
This study identifies activation characteristics of PPD-responsive T-cells that emerge after treatment with anti-CD4 monoclonal antibody (Mab). PPD-stimulated T-cell proliferations, OX40 phenotype and protein tyrosine phosphorylations involving p56lck (pp56lck) were compared to Con A stimulations using T-cells isolated from spleen and draining lymph node of CFA/PPD-immunized rats either untreated or treated in vivo with anti-CD4 Mab. Splenocytes stimulated by concanavalin A (Con A) showed correlated increases in proliferation, levels of pp56lck, and OX40 expression; these parameters were not correlated in splenocytes after PPD-stimulations. T-cells isolated from lymph nodes draining the site of CFA/PPD immunization proliferated in response to stimulation by either PPD or Con A, but only PPD-responsive cells showed correlation to the OX40 activation phenotype and increased levels of pp56lck. CD4+ T-cells isolated from either tissue compartment after anti-CD4 Mab treatments showed higher background and PPD-stimulated proliferations, and expressed lower levels of OX40. In contrast, anti-CD4 Mab treatments reduced (60%) and abolished Con A-stimulated proliferations of splenocytes and lymph node T-cells, respectively. The effects of anti-CD4 Mab treatment on pp56lck levels correlated only to the changes observed for Con A stimulations of splenocytes. These results demonstrate that PPD antigen-specific T-cell populations recovered from different tissue compartments were resistant to in vivo anti-CD4 Mab treatments and did not show the activation changes characteristics of CD4+ T-cells after Con A stimulation.
本研究确定了用抗CD4单克隆抗体(Mab)治疗后出现的PPD反应性T细胞的激活特征。将PPD刺激的T细胞增殖、OX40表型和涉及p56lck(pp56lck)的蛋白酪氨酸磷酸化与使用从CFA/PPD免疫大鼠的脾脏和引流淋巴结中分离的T细胞进行的Con A刺激进行比较,这些大鼠未接受治疗或在体内用抗CD4 Mab治疗。伴刀豆球蛋白A(Con A)刺激的脾细胞在增殖、pp56lck水平和OX40表达方面呈现相关增加;在PPD刺激后的脾细胞中,这些参数不相关。从CFA/PPD免疫部位引流的淋巴结中分离的T细胞对PPD或Con A刺激有反应而增殖,但只有PPD反应性细胞显示与OX40激活表型相关且pp56lck水平增加。抗CD4 Mab治疗后从任一组织区室分离的CD4 + T细胞显示出更高的背景和PPD刺激的增殖,并表达较低水平的OX40。相反,抗CD4 Mab治疗分别降低了(60%)和消除了脾细胞和淋巴结T细胞的Con A刺激的增殖。抗CD4 Mab治疗对pp56lck水平的影响仅与脾细胞Con A刺激所观察到的变化相关。这些结果表明,从不同组织区室中回收的PPD抗原特异性T细胞群体对体内抗CD4 Mab治疗具有抗性,并且在Con A刺激后未显示出CD4 + T细胞的激活变化特征。