Waldmann T A, Broder S, Durm M, Blackman M, Krakauer R, Meade B
Trans Assoc Am Physicians. 1975;88:120-34.
The nature of the immunological defect in patients with hypogammaglobulinemia associated with a thymoma was investigated using a technique established to study the differentiation of lymphocytes into immunoglobulin synthesizing and secreting cells. Exhaustively washed peripheral blood lymphocytes were cultured for 7 days in RPMI-1640 medium supplemented with fetal calf serum in the presence of the lectin, pokeweed mitogen. The IgG, IgA, and IgM synthesized and secreted into the medium were measured by competitive double antibody radio-immunoassays. Twenty-two normal individuals synthesized 1625 ng of IgG, 1270 ng of IgA, and 4910 ng of IgM per 2 million lymphocytes in culture. In contrast, the three patients with hypogammaglobulinemia and a thymoma synthesized less than 100 ng of each class of immunoglobulin. When lymphocytes from 2 of the 3 patients studied were cocultured with normal lymphocytes and pokeweed mitogen, the synthesis of immunoglobulin by normal lymphocytes was depressed by a factor of 66 to 97%. Co-cultue of purified T cells from the hypogammaglobulinemic patients with normal lymphocytes resulted in an 87% suppression of immunoglobulin synthesis by the normal cells. However, no suppression of immunoglobulin synthesis was observed when preparations of B cells and macrophages depleted of T cells from the hypogammaglobulinemic patients were co-cultured with normal lymphocytes. In addition, in control studies no such suppression of immunoglobulin synthesis was seen when normal cells were co-cultured with lymphocytes from unrelated normals, patients with isolated IgA deficiency, patients with chronic lymphocytic leukemia or patients with the Sezary syndrome, a T cell leukemia nor were they inhibited when incubated with T cells from unrelated normals. These observations suggest that in some patients the hypogammaglobulinemia associated with a thymoma may be caused or perpetuated by an abnormality of regulatory T cells which suppress the maturation of lymphocytes into antibody producing cells.
采用一种已确立的研究淋巴细胞分化为免疫球蛋白合成和分泌细胞的技术，对与胸腺瘤相关的低丙种球蛋白血症患者的免疫缺陷性质进行了研究。将充分洗涤后的外周血淋巴细胞在补充有胎牛血清的RPMI-1640培养基中，于植物血凝素（商陆有丝分裂原）存在的情况下培养7天。通过竞争性双抗体放射免疫测定法测量合成并分泌到培养基中的IgG、IgA和IgM。22名正常个体每200万培养淋巴细胞合成1625 ng IgG、1270 ng IgA和4910 ng IgM。相比之下，3名患有低丙种球蛋白血症和胸腺瘤的患者每类免疫球蛋白的合成量均少于100 ng。当所研究的3名患者中的2名患者的淋巴细胞与正常淋巴细胞及商陆有丝分裂原共培养时，正常淋巴细胞的免疫球蛋白合成被抑制了66%至97%。低丙种球蛋白血症患者的纯化T细胞与正常淋巴细胞共培养导致正常细胞的免疫球蛋白合成被抑制87%。然而，当将低丙种球蛋白血症患者的不含T细胞的B细胞和巨噬细胞制剂与正常淋巴细胞共培养时，未观察到免疫球蛋白合成受到抑制。此外，在对照研究中，当正常细胞与无关正常个体的淋巴细胞、孤立性IgA缺乏症患者的淋巴细胞、慢性淋巴细胞白血病患者的淋巴细胞或Sezary综合征（一种T细胞白血病）患者的淋巴细胞共培养时，未见到这种免疫球蛋白合成的抑制现象，正常细胞与无关正常个体的T细胞孵育时也未受到抑制。这些观察结果表明，在一些患者中，与胸腺瘤相关的低丙种球蛋白血症可能是由调节性T细胞异常引起或持续存在的，这种异常抑制淋巴细胞成熟为抗体产生细胞。
