Winfield J B, Shaw M, Minota S
J Immunol. 1986 May 1;136(9):3246-53.
Cold-reactive lymphocytotoxic autoantibodies are present in the serum of most patients with active systemic lupus erythematosus (SLE) and may be important for the development of the lymphopenia and T cell dysfunction characteristic of this disorder. Neither the mechanisms of autoantibody action in this regard, nor the nature of the relevant T cell membrane target molecules have been defined, however. In the present investigation, preincubation of T cells with SLE serum at 37 degrees C reduced their reactivity with SLE IgM anti-lymphocyte autoantibodies, as demonstrated by indirect immunofluorescence and complement-dependent cytotoxicity. Modulation was restricted to SLE IgM autoantibody-reactive antigen; monoclonal antibody staining of various T cell differentiation and activation antigens remained unchanged. Loss of antigen from the surface membrane was rapid, but transient. A nadir was reached after approximately 120 min of 37 degrees C incubation, followed by essentially complete reexpression of antigen several hours later. Although modulation occurred spontaneously at 37 degrees C in the absence of SLE serum, loss of antigen was enhanced by IgM anti-lymphocyte autoantibodies, despite their low thermal amplitude. Modulation was inhibited by sodium azide, by fixation of cells with paraformaldehyde, and by low incubation temperatures. Colchicine and cytochalasin D had no effect on this process, suggesting that the integrity of the cytoskeleton was not essential. Cycloheximide did not prevent loss of antigen, but inhibited its reexpression. In experiments to determine the fate of modulated antigen, both intracytoplasmic accumulation and shedding from the cell surface were demonstrated. Only shedding was increased by the presence of anti-lymphocyte antibodies, however. These studies delineate modulation of T cell membrane antigen as a new mechanism for anti-lymphocyte autoantibody action in SLE. The occurrence of modulation at physiologic temperatures in vitro suggests that a similar phenomenon of potential relevance to T cell dysfunction may obtain in patients with this disorder.
冷反应性淋巴细胞毒性自身抗体存在于大多数活动性系统性红斑狼疮（SLE）患者的血清中，可能对该疾病特有的淋巴细胞减少和T细胞功能障碍的发展具有重要意义。然而，在这方面自身抗体作用的机制以及相关T细胞膜靶分子的性质均未明确。在本研究中，如间接免疫荧光和补体依赖性细胞毒性所示，T细胞在37℃下与SLE血清预孵育会降低其与SLE IgM抗淋巴细胞自身抗体的反应性。调节作用仅限于SLE IgM自身抗体反应性抗原；各种T细胞分化和激活抗原的单克隆抗体染色保持不变。表面膜上抗原的丢失迅速，但具有短暂性。在37℃孵育约120分钟后达到最低点，数小时后抗原基本完全重新表达。尽管在没有SLE血清的情况下，37℃时会自发发生调节作用，但IgM抗淋巴细胞自身抗体仍会增强抗原的丢失，尽管它们的热幅度较低。叠氮化钠、用多聚甲醛固定细胞以及低温孵育均可抑制调节作用。秋水仙碱和细胞松弛素D对该过程无影响，表明细胞骨架的完整性并非必需。放线菌酮不能阻止抗原的丢失，但会抑制其重新表达。在确定被调节抗原命运的实验中，证明了抗原在细胞质内的积累和从细胞表面的脱落。然而，只有脱落会因抗淋巴细胞抗体的存在而增加。这些研究将T细胞膜抗原的调节描述为SLE中抗淋巴细胞自身抗体作用的一种新机制。体外在生理温度下发生调节作用表明，在该疾病患者中可能存在与T细胞功能障碍潜在相关的类似现象。
