Roelen Dave L, van Bree Simone, van Hulst Paula, van Beelen Els, Claas Frans H J
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
Hum Immunol. 2002 Oct;63(10):902-11. doi: 10.1016/s0198-8859(02)00453-6.
Pretransplant blood transfusions sharing one human leukocyte antigen DR (HLA-DR) with the recipient have been shown to enhance graft survival, whereas HLA-DR mismatched blood transfusions will lead to immunization of the patient. The involvement of self HLA-DR suggests a role for CD4(+) regulatory T cells recognizing allopeptides in the context of self HLA class II molecules. Specific immunoregulation may be due to recognition of these allopeptides in the DR molecules of autologous T cells or dendritic cells. We tested this hypothesis on the basis of the reactivity of cell line ThoU6 which recognizes a peptide derived from an allo DR3 molecule, in the context of self DPB10301, and EL26, a CD4(+) T-cell clone recognizing HLA-A2 peptide in the presence of DRB11501. Addition of the line and clone to an assay in which the alloreactive cytotoxic T cell response (in a limiting dilution analysis) of PBLs sharing the restriction element was measured, resulted in a suppression of the anti-donor response but only when the proper peptide was added. These regulatory CD4(+) T cells were cytotoxic for targets presenting the proper peptide in the context of self MHC class II. Furthermore, these cells produced IL-10 after stimulation with the specific MHC/peptide combinations. Despite the similarity in function, EL26 and ThoU6 showed some differences in their phenotypic characteristics. Although both were CD25(+), EL26 expressed surface TGF-beta and CTLA-4, while ThoU6 did not. Similar regulatory T cells may explain the enhanced graft survival after HLA-DR shared blood transfusions either by their interaction with autologous alloreactive T cells or by modulation of autologous dendritic cells presenting the peptide involved.
研究表明，移植前与受者共享一种人类白细胞抗原DR（HLA - DR）的输血可提高移植物存活率，而HLA - DR不匹配的输血则会导致患者免疫。自身HLA - DR的参与表明CD4(+)调节性T细胞在自身HLA II类分子背景下识别异源肽发挥了作用。特异性免疫调节可能是由于在自体T细胞或树突状细胞的DR分子中识别这些异源肽。我们基于细胞系ThoU6（在自身DPB10301背景下识别源自同种异体DR3分子的肽）和EL26（在DRB11501存在下识别HLA - A2肽的CD4(+) T细胞克隆）的反应性来验证这一假设。将该细胞系和克隆添加到一个检测中，该检测用于测量共享限制元件的外周血淋巴细胞的同种异体反应性细胞毒性T细胞反应（在有限稀释分析中），结果导致抗供体反应受到抑制，但前提是添加了合适的肽。这些调节性CD4(+) T细胞对在自身MHC II类背景下呈递合适肽的靶细胞具有细胞毒性。此外，这些细胞在用特定的MHC/肽组合刺激后会产生IL - 10。尽管功能相似，但EL26和ThoU6在表型特征上存在一些差异。虽然两者都是CD25(+)，但EL26表达表面TGF - β和CTLA - 4，而ThoU6不表达。类似的调节性T细胞可能通过与自体同种异体反应性T细胞相互作用或通过调节呈递相关肽的自体树突状细胞来解释HLA - DR共享输血后移植物存活率提高的现象。
