Frasca L, Marelli-Berg F, Imami N, Potolicchio I, Carmichael P, Lombardi G, Lechler R
Department of Immunology, Royal Postgraduate Medical School, London, England, United Kingdom.
Kidney Int. 1998 Mar;53(3):679-89. doi: 10.1046/j.1523-1755.1998.00800.x.
Following organ transplantation, tissue parenchymal cells commonly express major histocompatibility complex (MHC) class II molecules as a result of local cytokine release, and thus acquire the capacity to present donor MHC alloantigens to alloreactive CD4+ T cells. The consequences of such a presentation are likely to be relevant in the induction of tolerance to the transplanted tissues, and this has been reported in animal models of transplantation and in humans. In this study, the consequences of antigen presentation by interferon-gamma (IFN-gamma)-treated human renal tubular epithelial cells (RTEC) to resting and activated CD4+ T cells were investigated. Allogeneic RTEC were unable to stimulate proliferation by peripheral blood CD45 RA+ or RO+ CD4+ T cells from three HLA-mismatched responders. The response to RTEC was partially reconstituted by the addition of murine L cell transfectants expressing human B7.1 (DAP.3-B7), suggesting that the failure of RTEC to stimulate a primary alloresponse was due, at least in part, to a lack of costimulation. T cell clones dependent on B7-mediated co-stimulation also did not respond to peptide presented by RTEC. Most importantly, this lack of reactivity was accompanied by the induction of nonresponsiveness. Incubation with allogeneic, DR-expressing RTEC induced allospecific hyporesponsiveness in both CD45RA+ and RO+ cells. Similarly, overnight incubation with antigen-pulsed RTEC induced nonresponsiveness in the B7-dependent T cell clones. These results suggest that MHC class II expression on RTEC may contribute to the induction of an allospecific nonresponsiveness following organ transplantation.
器官移植后，由于局部细胞因子的释放，组织实质细胞通常会表达主要组织相容性复合体（MHC）II类分子，从而获得将供体MHC同种异体抗原呈递给同种反应性CD4 + T细胞的能力。这种呈递的后果可能与诱导对移植组织的耐受性有关，这在移植动物模型和人类中已有报道。在本研究中，研究了经干扰素-γ（IFN-γ）处理的人肾小管上皮细胞（RTEC）向静息和活化的CD4 + T细胞呈递抗原的后果。来自三名HLA不匹配应答者的外周血CD45 RA +或RO + CD4 + T细胞，对同种异体RTEC无增殖刺激反应。通过添加表达人B7.1的鼠L细胞转染子（DAP.3-B7），对RTEC的反应得到部分重建，这表明RTEC不能刺激初次同种反应，至少部分是由于缺乏共刺激。依赖B7介导的共刺激的T细胞克隆，对RTEC呈递的肽也无反应。最重要的是，这种无反应性伴随着无反应状态的诱导。与同种异体、表达DR的RTEC孵育，可诱导CD45RA +和RO +细胞产生同种特异性低反应性。同样，与抗原脉冲RTEC过夜孵育，可诱导B7依赖性T细胞克隆产生无反应性。这些结果表明，RTEC上的MHC II类表达可能有助于器官移植后诱导同种特异性无反应性。
