Alard Pascale, Clark Sherry L, Kosiewicz Michele M
Department of Microbiology and Immunology, University of Louisville Health Sciences Center, KY 40202, USA.
Eur J Immunol. 2004 Apr;34(4):1021-30. doi: 10.1002/eji.200324547.
Transforming growth factor beta (TGF beta)-treated antigen-presenting cells (APC) pulsed with antigen induce tolerance in mice, i.e. inhibition of IFN-gamma production and delayed type hypersensitivity response. Although evidence suggests that regulatory T cells are involved, their mechanism of action is currently unknown and is the subject of the present study. Both CD4 and CD8 splenic T cells from mice injected i.v. with adherent thioglycolate-elicited peritoneal exudate cells cultured with TGF beta(2) and antigen (TGF beta-treated APC) transferred tolerance to naive recipients. Interestingly, TGF beta-treated APC from class II knockout mice were unable to induce tolerance in wild-type mice, whereas wild-type TGF beta-treated APC could induce tolerance in CD8 knockout mice. TGF beta was detected in cultures of lymphoid cells from mice injected with TGF beta-treated APC, and treatment with anti-TGF beta antibody in vivo impaired tolerance induction. TGF beta appeared to be involved in both the development of CD4 regulatory T cells and the effector function of the CD4 regulatory T cells. In summary, the important findings in this study are that CD4, and not CD8, regulatory T cells are required for tolerance induced by TGF beta-treated APC in naive mice, and tolerance appears to be mediated by a mechanism involving TGF beta.
用抗原脉冲处理的转化生长因子β（TGF-β）处理的抗原呈递细胞（APC）可诱导小鼠产生耐受性，即抑制γ干扰素的产生和迟发型超敏反应。尽管有证据表明调节性T细胞参与其中，但其作用机制目前尚不清楚，是本研究的主题。经静脉注射用TGF-β2和抗原培养的贴壁巯基乙酸盐诱导的腹膜渗出细胞（TGF-β处理的APC）处理的小鼠的CD4和CD8脾T细胞，可将耐受性转移给未接触过抗原的受体。有趣的是，来自II类敲除小鼠的TGF-β处理的APC无法在野生型小鼠中诱导耐受性，而野生型TGF-β处理的APC可在CD8敲除小鼠中诱导耐受性。在注射了TGF-β处理的APC的小鼠的淋巴细胞培养物中检测到TGF-β，体内用抗TGF-β抗体处理会损害耐受性诱导。TGF-β似乎参与了CD4调节性T细胞的发育以及CD4调节性T细胞的效应功能。总之，本研究的重要发现是，在未接触过抗原的小鼠中，TGF-β处理的APC诱导的耐受性需要CD4而非CD8调节性T细胞，并且耐受性似乎是由涉及TGF-β的机制介导的。
