Oral Tolerance Induction by Type V Collagen in Lung Transplantation

目的：肺移植排斥反应涉及对V型胶原的免疫应答[col（V）]。由col（V）诱导的口服耐受消除了对供体抗原的迟发型超敏反应（DTH），并防止了急性和慢性肺移植排斥反应。这些数据表明col（V）诱导的耐受性可能刺激了抑制排斥反应的调节性T细胞。本研究的目的是确定col（V）口服耐受性是否诱导调节性T细胞，并确定利用F344肺同种异体移植物（RT 1 ^）原位移植到WKY（RT 1 ^1）大鼠受体中由这些细胞诱导的免疫抑制机制<lv1>。我们利用了我们最近描述的col（V）诱导的对肺同种异体移植物的口服耐受的模型，其中在移植前给WKY大鼠喂食col（V）诱导对F344肺同种异体移植物的耐受。从不同组的WKY大鼠（包括耐受大鼠）的脾脏中纯化CD 4+和CD 8 + T细胞，并用于过继转移研究。DTH反应和排斥反应的病理进行了评估，在不同组的过继transferred animals.Results：数据显示，过继转移的CD 4+，但不CD 8+，T细胞从耐受大鼠未处理的同种异体移植受体废除DTH反应供体抗原，并防止急性和慢性肺移植排斥反应。MLR显示耐受大鼠的CD 4 + T细胞组成性地产生TGF-β，并响应同种异体抗原。最后，抗TGF-β抗体恢复了由过继转移的“耐受性”CD 4 + T细胞抑制的DTH应答。结论：我们得出结论：col（V）诱导的口服耐受导致调节性CD 4 + T细胞的活性，其通过产生TGF-β抑制同种异体反应性。

Objective : Lung allograft rejection involves an immune response to type V collagen [col(V)]. Oral tolerance induced by col(V) abrogates delayed type hypersensitivity (DTH) responses to donor antigens, and prevented acute and chronic lung allograft rejection. These data suggest that col(V)-induced tolerance might have stimulated regulatory T cells that suppress rejection responses. The purpose of the current study was to determine if col(V) oral tolerance induced regulatory T cells, and to determine the mechanism of immune suppression induced by these cells utilizing F344 lung allografts (RT1^<lv1> for orthotopic transplantation into WKY (RT1^1) rat recipients.Materials and Methods : We utilized our recently described model of col(V)-induced oral tolerance to lung allografts in which feeding col(V) to WKY rats prior to transplantation induced tolerance to F344 lung allografts. CD4+ and CD8+ T cells were purified from spleens of different groups of WKY rats including tolerant rats and used for adoptive transfer studies. DTH responses and rejection pathology were assessed in different groups of adoptively transferred animals.Results : Data showed that adoptive transfer of CD4+, but not CD8+, T cells from tolerant rats to untreated allograft recipients abrogated DTH responses to donor antigens, and prevented acute and chronic lung allograft rejection. MLR's revealed that CD4+ T cells from tolerant rats produced TGF-β constitutively and in response to alloantigen. Finally, anti- TGF-β antibodies recovered DTH responses suppressed by adoptive transfer of "tolerant" CD4+ T cells.Conclusion : We conclude that col(V)-induced oral tolerance results in activity of regulatory CD4+ T cells that suppress alloreactivity by production of TGF-β.