REGULATION OF CYTOTOXIC T LYMPHOCYTE‐MEDIATED GRAFT REJECTION FOLLOWING BONE MARROW
REGULATION OF CYTOTOXIC T LYMPHOCYTE‐MEDIATED GRAFT REJECTION FOLLOWING BONE MARROW
复制标题
细胞毒性 T 淋巴细胞介导的骨髓移植排斥的调节
作者：
B. Bierer;S. Emerson;J. Antin;R. Maziarz;J. Rappeport;B. Smith;A. .. Burakoff
细胞毒性T淋巴细胞被认为是介导人异基因骨髓移植后移植物排斥反应的效应细胞。我们已经研究了一个BMT患者谁拒绝单倍体相合T细胞耗尽骨髓。体外研究表明，循环淋巴细胞为受体来源的CD 3+和CD 8+，并对供体特异性I类主要组织相容性复合体抗原表现出选择性细胞毒性。细胞毒性被针对T细胞上的CD 3、CD 8、CD 2和淋巴细胞功能相关抗原-1以及针对靶细胞上的MHC I类蛋白的单克隆抗体抑制。此外，这些循环细胞抑制体外生长和分化的富集供体骨髓祖细胞，抑制部分逆转抗CD 3单克隆抗体。供者特异性免疫缺陷细胞衍生的CTL可介导移植抵抗，CTL活性可被许多单克隆抗体抑制。这些研究结果的主机准备和治疗的影响进行了讨论。
Cytotoxic T lymphocytes have been implicated as the effector cell mediating graft rejection following human allogeneic bone marrow transplantation. We have studied a BMT patient who rejected haploidentical T cell-depleted marrow. In vitro studies demonstrated that the circulating lymphocytes were CD3+ and CD8+, of recipient origin, and exhibited selective cytotoxicity against donor-specific class I major histocompatibility complex antigens. Cytotoxicity was inhibited by monoclonal antibodies directed against CD3, CD8, CD2, and lymphocyte function-associated antigen-1 on the T cell, and against MHC class I proteins on the target cell. Furthermore, these circulating cells inhibited the in vitro growth and differentiation of enriched donor bone marrow progenitor cells, an inhibition that was partially reversed by anti-CD3 MAb. Donor-specific recipient-derived CTL may mediate resistance to engraftment, and CTL activity may be inhibited by a number of MAb. The implications of these findings for host preparation and treatment are discussed.