Trembleau S, Penna G, Bosi E, Mortara A, Gately M K, Adorini L
Roche Milano Ricerche, Italy.
J Exp Med. 1995 Feb 1;181(2):817-21. doi: 10.1084/jem.181.2.817.
T cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. Administration of interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4+ T cells, induces rapid onset of IDDM in NOD, but not in BALB/c mice. Histologically, IL-12 administration induces massive infiltration of lymphoid cells, mostly T cells, in the pancreatic islets of NOD mice. CD4+ pancreas-infiltrating T cells, after activation by insolubilized anti T cell receptor antibody, secrete high levels of interferon gamma and low levels of IL-4. Therefore, IL-12 administration accelerates IDDM development in genetically susceptible NOD mice, and this correlates with increased Th1 cytokine production by islet-infiltrating cells. These results hold implications for the pathogenesis, and possibly for the therapy of IDDM and of other Th1 cell-mediated autoimmune diseases.
T细胞在非肥胖糖尿病（NOD）小鼠的胰岛素依赖型糖尿病（IDDM）发病过程中起主要作用。白细胞介素12（IL-12）是指导1型辅助性T（Th1）CD4 + T细胞发育的关键细胞因子，给予IL-12可使NOD小鼠迅速发生IDDM，但对BALB / c小鼠无此作用。组织学上，给予IL-12可诱导NOD小鼠胰岛中大量淋巴细胞浸润，主要是T细胞。经不溶性抗T细胞受体抗体激活后，浸润胰腺的CD4 + T细胞分泌高水平的干扰素γ和低水平的IL-4。因此，给予IL-12可加速遗传易感NOD小鼠的IDDM发展，这与胰岛浸润细胞产生的Th1细胞因子增加有关。这些结果对IDDM以及其他Th1细胞介导的自身免疫性疾病的发病机制乃至治疗都具有启示意义。
