Kramer J K, Depew W T, Szewczuk M R
Gastrointestinal Disease Research Unit, Hotel Dieu Hospital, Kingston, Ontario, Canada.
J Clin Lab Immunol. 1988 Jan;25(1):19-27.
In a recent study, we have shown that peripheral blood B cells from patients with ulcerative colitis (UC) synthesized less immunoglobulin (Ig) in co-culture with autologous T cells than normal adults' B cells. When UC patients' T cells were co-cultured with normal adults' B cells, Ig synthesis was significantly decreased as compared with normal controls. In contrast, Crohn's disease (CD) patients' B and T cells functioned normally. In the present study, the activity of suppressor T cells in patients with UC and CD was determined. Peripheral blood B and T cells with monocytes were obtained from patients and normal adults of the same age and sex, and co-cultured for 10 days with pokeweed mitogen (PWM). Suppressor T-cell function was measured in mixed co-culture assays in which graded numbers of normal or patient's T cells were added to normal adults' B and T cells with PWM. Immunoglobulins (Ig) M, G and A were measured in culture supernatants using a sensitive enzyme-linked immunosorbent assay. The quantity of Ig present in the culture supernatants was determined from a standard curve. T cells from UC patients significantly decreased immunoglobulin production by control B and T cells (IgM and IgA, p = 0.02; IgG, p = 0.01). In contrast, addition of T cells from CD patients produced no significant differences. Complement mediated, monoclonal OKT8 antibody directed cell lysis revealed that the inhibition observed with UC patients' T cells in co-culture was due to a T8+ suppressor T cell. The degree of inhibition of immunoglobulin synthesis did not correlate with disease activity, duration of illness, location of disease, or corticosteroid treatment. Thus, patients with ulcerative colitis display enhanced suppressor T-cell activity in peripheral blood while patients with CD show normal helper and suppressor T-cell functions. These results provide evidence supporting a role for altered immunoregulatory activity in the pathogenesis of ulcerative colitis.
在最近的一项研究中，我们发现，与正常成年人的B细胞相比，溃疡性结肠炎（UC）患者的外周血B细胞在与自体T细胞共培养时合成的免疫球蛋白（Ig）较少。当UC患者的T细胞与正常成年人的B细胞共培养时，与正常对照组相比，Ig合成显著减少。相比之下，克罗恩病（CD）患者的B细胞和T细胞功能正常。在本研究中，测定了UC和CD患者中抑制性T细胞的活性。从年龄和性别相同的患者及正常成年人中获取外周血B细胞、T细胞和单核细胞，并与商陆有丝分裂原（PWM）共培养10天。在混合共培养试验中测量抑制性T细胞功能，即将不同数量的正常或患者T细胞加入到含有PWM的正常成年人B细胞和T细胞中。使用灵敏的酶联免疫吸附测定法测量培养上清液中的免疫球蛋白（Ig）M、G和A。根据标准曲线确定培养上清液中Ig的含量。UC患者的T细胞显著降低了对照B细胞和T细胞的免疫球蛋白产生（IgM和IgA，p = 0.02；IgG，p = 0.01）。相比之下，加入CD患者的T细胞未产生显著差异。补体介导的、单克隆OKT8抗体介导的细胞裂解显示，在共培养中观察到的UC患者T细胞的抑制作用是由T8 +抑制性T细胞引起的。免疫球蛋白合成的抑制程度与疾病活动度、病程、疾病部位或皮质类固醇治疗无关。因此，溃疡性结肠炎患者外周血中抑制性T细胞活性增强，而CD患者的辅助性T细胞和抑制性T细胞功能正常。这些结果为免疫调节活性改变在溃疡性结肠炎发病机制中的作用提供了证据支持。
