Santambrogio L, Hochwald G M, Leu C H, Thorbecke G J
Department of Pathology, NYU School of Medicine, NY 10016.
Immunopharmacol Immunotoxicol. 1993 Aug;15(4):461-78. doi: 10.3109/08923979309035240.
Injection of transforming growth factor beta 1 (TGF-beta 1) for five days during the late phase of the immunization process leading either to collagen type II induced arthritis (CIA) or to experimental allergic encephalomyelitis (EAE) protects against the development of these auto-immune diseases. Tumor necrosis factor alpha (TNF-alpha) injected during this same interval aggrevates CIA. In addition, anti-TGF-beta exacerbates and anti-TNF protects against CIA, acute and relapsing EAE, suggesting an important regulatory role for the endogenous production of the two cytokines on the severity of these diseases. More detailed studies about the mechanism of action of TGF-beta in acute EAE show that there is no detectable effect of TGF-beta on the development of sensitized T cells in vivo, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood to myelin antigens. Nevertheless, the number of lymphoid cells infiltrating the central nervous tissue is much greater in untreated than in TGF-beta-treated, protected mice. We conclude that it is likely that TGF-beta protects against experimental auto-immune diseases by interfering with the entry of lymphoid cells into the target organs through inhibition of the upregulation of adhesion molecule expression on endothelial cells, and with subsequent inflammatory processes inside the target organs by antagonizing both the production and the effects of TNF.
在导致胶原诱导性关节炎（CIA）或实验性自身免疫性脑脊髓炎（EAE）的免疫过程后期，注射转化生长因子β1（TGF-β1）五天可预防这些自身免疫性疾病的发生。在同一时间段内注射肿瘤坏死因子α（TNF-α）会加重CIA。此外，抗TGF-β会加剧CIA，而抗TNF则可预防CIA、急性和复发性EAE，这表明内源性产生的这两种细胞因子对这些疾病的严重程度具有重要的调节作用。关于TGF-β在急性EAE中作用机制的更详细研究表明，通过检测来自淋巴结和外周血的T细胞对髓磷脂抗原的增殖反应，发现TGF-β在体内对致敏T细胞的发育没有可检测到的影响。然而，未治疗的小鼠与经TGF-β治疗得到保护的小鼠相比，浸润中枢神经组织的淋巴细胞数量要多得多。我们得出结论，TGF-β可能通过抑制内皮细胞上黏附分子表达的上调来干扰淋巴细胞进入靶器官，并通过拮抗TNF的产生及其作用来对抗靶器官内随后发生的炎症过程，从而预防实验性自身免疫性疾病。
