Kunicka J E, Platsoucas C D
Memorial Sloan-Kettering Cancer Center, New York.
Blood. 1988 Jun;71(6):1551-60.
We investigated helper and suppressor functions to B-cell responses and T-T cell interactions of purified T4 and T8 cells from 20 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Appropriate mixtures of purified T4 or T8 cells from patients with CLL were cultured with purified B cells or T4 and B cells from normal donors for 7 days with pokeweed mitogen (PWM). IgM, IgA, and IgG produced were determined in the supernatants of these cultures by a heavy chain-specific enzyme-linked immunosorbent assay (ELISA) and compared to those obtained by the corresponding mixtures of T4, T8, and B cells from normal donors. Purified T4 cells from 14 of 20 patients with CLL exhibited defective helper function (P less than .001) to immunoglobulin (Ig) production by purified B cells from normal donors. Purified T4 cells from 6 of these 14 patients were able to suppress significantly (P less than .001) and in a concentration-dependent manner Ig production by mixtures of T4 and B cells from normal donors, in the absence of T8 cells. These suppressor effector T4 cells from certain patients were partially radiosensitive. Purified T8 cells from 8 of 20 patients with CLL exhibited excessive suppressor activity. These cells significantly suppressed (P less than .001), Ig production by mixtures of T4 and B cells from normal donors to a degree significantly higher (P less than .005) than that observed by equal numbers of T8 cells from normal donors. This inhibition was dependent on the numbers of the T8 CLL cells added to the cultures. Excessive suppressor activity by T8 CLL cells was at least in part radiosensitive in four of eight patients. These results demonstrate a wide range of immunoregulatory T-cell abnormalities in patients with CLL. Naturally occurring T4 suppressor effector cells, directly inhibiting Ig production by mixtures of T4 and B cells, in the absence of T8 cells, are present in certain patients with CLL.
我们研究了20例未经治疗的B细胞慢性淋巴细胞白血病(CLL)患者纯化的T4和T8细胞对B细胞反应的辅助和抑制功能以及T-T细胞相互作用。将来自CLL患者的纯化T4或T8细胞与来自正常供体的纯化B细胞或T4和B细胞适当混合,用美洲商陆丝裂原(PWM)培养7天。通过重链特异性酶联免疫吸附测定(ELISA)测定这些培养物上清液中产生的IgM、IgA和IgG,并与来自正常供体的T4、T8和B细胞的相应混合物所获得的结果进行比较。20例CLL患者中有14例的纯化T4细胞对来自正常供体的纯化B细胞产生免疫球蛋白(Ig)的辅助功能存在缺陷(P<0.001)。在这14例患者中有6例的纯化T4细胞能够在没有T8细胞的情况下,显著抑制(P<0.001)且呈浓度依赖性地抑制来自正常供体的T4和B细胞混合物产生Ig。来自某些患者的这些抑制效应T4细胞具有部分放射敏感性。20例CLL患者中有8例的纯化T8细胞表现出过度的抑制活性。这些细胞显著抑制(P<0.001)来自正常供体的T4和B细胞混合物产生Ig,其抑制程度明显高于(P<0.005)来自正常供体的等量T8细胞所观察到的抑制程度。这种抑制作用取决于添加到培养物中的T8 CLL细胞数量。在8例患者中有4例,T8 CLL细胞的过度抑制活性至少部分具有放射敏感性。这些结果表明CLL患者存在广泛的免疫调节性T细胞异常。某些CLL患者中存在天然的T4抑制效应细胞,在没有T8细胞的情况下,直接抑制T4和B细胞混合物产生Ig。