Immunological tolerance regulated by the interaction between T cell and antigen-presenting cell

在自身免疫、变态反应性和感染性疾病以及移植物抗宿主病等T细胞介导的疾病中，炎症部位存在OX40~+淋巴细胞和OX40配体^+(OX40L)^+细胞。这些观察表明OX40-OX40L相互作用在免疫疾病中发挥重要作用。CD25~+CD_4~+调节性T细胞(Treg)通过控制外周自身反应性T细胞的激活来抑制自身免疫。最近，一些报道显示OX40在小鼠的Treg细胞上优先表达在mRNA和蛋白表达方面。因此，我们研究了OX40-OX40L相互作用是否可能控制Treg细胞的功能，这是预防自身免疫所必需的。我们通过使用OX40L缺乏的小鼠和过度表达OX40L的小鼠发现，当CD25^-CD4^+T细胞暴露在表达OX40L的细胞中时，或者当他们被激动型OX40特异性单抗处理时，CD25^-CD4^+T细胞对Treg介导的抑制变得不敏感。OX40信号也可以在炎症性肠病的实验模型中取消Treg细胞的疾病预防活性，该模型使用表达不同水平OX40L的RAG2缺陷小鼠。因此，这些数据表明，当OX40信号被直接传递到抗原结合的初始T细胞时，它们可以对抗Treg介导的抑制。综上所述，OX40信号直接控制Treg细胞介导的免疫抑制。

The presence of OX40^+ lymphocytes and OX40 ligand^+ (OX40L)^+ cells at the sites of inflammation in T cell-mediated disorders, such as autoimmunity, allergic and infectious diseases, and GVHD is well documented. These observations suggest important roles for OX40-OX40L interactions in immune disorders. CD25^+CD4^+ regulatory T (Treg) cells suppress autoinununity by controlling peripheral self-reactive T cell activation. Recently, several reports have revealed that OX40 is preferentially expressed on Treg cells in terms of mRNA and protein expression in mice. Thus we examined whether OX40-OX40L interaction may control Treg cell function that are essential for preventing autoimmunity.We found by using OX40L-deificient mice and mice overexpressing OX40L that CD25^-CD4^+ T cells became insensitive to Treg-mediated suppression when they were exposed to OX40L-expressing cells, or when they were treated with an agonistic OX40-specific monoclonal antibody. OX40 signaling could also abrogate the disease-preventing activity of Treg cells in an experimental model of inflammatory bowel disease using RAG2-deficient mice that expressed different levels of OX40L. Thus, these data show that OX40 signals can oppose Treg-mediated suppression when they are delivered directly to antigen-engaged naive T cells. Taken together, OX40 signaling directly control Treg-cell-mediated immune suppression.