Romagnani S, Del Prete G F, Maggi E, Bellesi G, Biti G, Rossi Ferrini P L, Ricci M
J Clin Invest. 1983 May;71(5):1375-82. doi: 10.1172/jci110890.
The immunoglobulin-synthesizing activities of peripheral blood mononuclear cells from 57 untreated patients with Hodgkin's disease and 47 normal subjects were compared. Cumulative amounts of IgM and IgG synthesized and secreted by unstimulated and pokeweed mitogen-stimulated cells over a 7-d period were determined in a solid-phase radioimmunoassay. Synthesis of IgM in unstimulated cultures and of both IgM and IgG in cultures stimulated with pokeweed mitogen was markedly reduced in patients with Hodgkin's disease, whereas the mean level of the spontaneous IgG synthesis was enhanced. The degree and frequency of in vitro abnormalities were not influenced by disease stage or histology. Depression of pokeweed mitogen-induced immunoglobulin synthesis did not correlate with excessive number of monocytes and it was unaffected by removal of phagocytic cells or addition to the cultures of monocytes from normal individuals. On the other hand, monocytes isolated from blood of patients with Hodgkin's disease were even more effective than normal monocytes in supporting pokeweed mitogen-induced immunoglobulin synthesis by normal phagocyte-depleted mononuclear cells. Synthesis of both IgM and IgG induced by pokeweed mitogen remained subnormal after addition to patient B cell cultures of autologous irradiated T cells or allogeneic normal T lymphocytes. T cells from patients with Hodgkin's disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkin's disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells to normal B cells resulted in an increase of spontaneous IgG synthesis. In patients showing depression of pokeweed mitogen-induced immunoglobulin synthesis the lymphoproliferative response and immunoglobulin synthesis stimulated by Staphylococcus aureus bacteria of the Cowan first strain, a T cell independent B cell mitogen, were also markedly reduced. These studies demonstrate impairment of immunoglobulin synthesis by cultured lymphocytes from untreated patients with Hodgkin's disease after stimulation with polyclonal B cell activators and suggest that the in vitro abnormalities may be, at least in part, the result of a preexisting in vivo activation of lymphocytes in Hodgkin's disease patients.
比较了57例未经治疗的霍奇金病患者和47名正常受试者外周血单个核细胞的免疫球蛋白合成活性。通过固相放射免疫测定法测定了在7天时间内未刺激和经商陆有丝分裂原刺激的细胞合成和分泌的IgM和IgG的累积量。霍奇金病患者未刺激培养物中IgM的合成以及经商陆有丝分裂原刺激培养物中IgM和IgG的合成均显著降低，而自发IgG合成的平均水平则升高。体外异常的程度和频率不受疾病分期或组织学的影响。商陆有丝分裂原诱导的免疫球蛋白合成受抑与单核细胞数量过多无关，去除吞噬细胞或向培养物中添加正常个体的单核细胞对其无影响。另一方面，从霍奇金病患者血液中分离的单核细胞在支持经正常吞噬细胞耗竭的单个核细胞进行商陆有丝分裂原诱导的免疫球蛋白合成方面，甚至比正常单核细胞更有效。在患者B细胞培养物中加入自体照射的T细胞或同种异体正常T淋巴细胞后，商陆有丝分裂原诱导的IgM和IgG合成仍低于正常水平。霍奇金病患者的T细胞在帮助正常B细胞进行商陆有丝分裂原诱导的免疫球蛋白产生方面似乎至少与正常T细胞一样有效。然而，当正常T细胞与霍奇金病患者的B细胞共培养时，自发IgG合成下降，而将患者T细胞添加到正常B细胞中则导致自发IgG合成增加。在表现出商陆有丝分裂原诱导免疫球蛋白合成受抑的患者中，由考恩I株金黄色葡萄球菌（一种T细胞非依赖性B细胞有丝分裂原）刺激的淋巴细胞增殖反应和免疫球蛋白合成也显著降低。这些研究表明，未经治疗的霍奇金病患者的培养淋巴细胞在受到多克隆B细胞激活剂刺激后免疫球蛋白合成受损，提示体外异常可能至少部分是霍奇金病患者体内预先存在的淋巴细胞激活的结果。
