Knobloch C, Goldmann S F, Friedrich W
Department of Pediatrics II, University Ulm, FRG.
Eur J Immunol. 1991 Oct;21(10):2479-87. doi: 10.1002/eji.1830211026.
We have analyzed allorecognition, HLA restriction and T cell receptor (TcR) diversity in an HLA-heterozygous (HLA-DRw6,7) severe combined immunodeficiency (SCID) patient whose T cell system had been repopulated by HLA-homozygous (HLA-DRw6) paternal T cells following T cell-depleted bone marrow transplantation (BMT). Donor origin of T cells and host origin of antigen-presenting cells (APC) in peripheral blood and BM is shown by HLA typing of separated cell populations and two-color immunofluorescence using an anti-HLA monoclonal antibody (mAb). Peripheral blood lymphocytes (PBL) from the chimeric patient proliferate normally against PHA, anti-TcR/CD3 mAb, pooled allogeneic PBL, and also against the recall antigen (Ag) tetanus toxoid and purified protein derivative of tuberculin (PPD) following immunization, suggesting recognition by donor (DRw6) T cells of Ag presented by host (DRw6,7) APC. PPD-specific cytotoxic T lymphocytes generated in vitro from patient PBL post-BMT display specific cytotoxicity against targets expressing DRw6 and DR7, but not against DR-mismatched targets, suggesting that HLA restriction of Ag recognition may occur through determinants expressed by the host and not by the donor. Donor T cells differentiated in the HLA-semiallogeneic host show specific proliferative and cytotoxic responses against HLA-mismatched stimulators, but not against stimulators taken from the host, expressing the host-specific HLA-haplotype, or expressing the host-specific HLA-DR7 antigens. Compared to T cells directly taken from the donor, differentiation of donor T cells in the host is associated with a significant decrease of T cells expressing TcR V beta 5 and V alpha 2 determinants, while no differences in the abundance of of TcR V beta 6, V beta 8 and V beta 12 subsets were noticed. We conclude that allorecognition, major histocompatibility complex (MHC) restriction and TcR diversity generation of human T cells can be modulated through differentiation in an MHC-different environment, as had been previously shown to be the case in murine model systems.
我们分析了一名 HLA 杂合子（HLA - DRw6,7）严重联合免疫缺陷（SCID）患者的同种异体识别、HLA 限制和 T 细胞受体（TcR）多样性。该患者在进行 T 细胞去除的骨髓移植（BMT）后，其 T 细胞系统由 HLA 纯合子（HLA - DRw6）的父源 T 细胞重新填充。通过对分离的细胞群体进行 HLA 分型以及使用抗 HLA 单克隆抗体（mAb）进行双色免疫荧光，显示外周血和骨髓中 T 细胞的供体来源以及抗原呈递细胞（APC）的宿主来源。嵌合患者的外周血淋巴细胞（PBL）对 PHA、抗 TcR/CD3 mAb、汇集的同种异体 PBL 正常增殖，并且在免疫后对回忆抗原（Ag）破伤风类毒素和结核菌素纯蛋白衍生物（PPD）也正常增殖，这表明供体（DRw6）T 细胞识别宿主（DRw6,7）APC 呈递的 Ag。BMT 后从患者 PBL 体外产生的 PPD 特异性细胞毒性 T 淋巴细胞对表达 DRw6 和 DR7 的靶细胞显示出特异性细胞毒性，但对 DR 不匹配的靶细胞无细胞毒性，这表明 Ag 识别的 HLA 限制可能通过宿主而非供体表达的决定簇发生。在 HLA 半同种异体宿主中分化的供体 T 细胞对 HLA 不匹配的刺激物显示出特异性增殖和细胞毒性反应，但对来自宿主、表达宿主特异性 HLA 单倍型或表达宿主特异性 HLA - DR7 抗原的刺激物无反应。与直接从供体获取的 T 细胞相比，宿主中供体 T 细胞的分化与表达 TcR Vβ5 和 Vα2 决定簇的 T 细胞显著减少相关，而未观察到 TcR Vβ6、Vβ8 和 Vβ12 亚群丰度的差异。我们得出结论，人类 T 细胞的同种异体识别、主要组织相容性复合体（MHC）限制和 TcR 多样性产生可通过在 MHC 不同的环境中分化来调节，正如先前在小鼠模型系统中所显示的那样。
