EFFECTS OF GRAFT VS HOST REACTIONS ON CELL-MEDIATED IMMUNITY

移植物抗宿主反应对细胞介导免疫的影响

• 批准号: 3813460
• 负责人: G M SHEARER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813460
• 关键词: CD4 molecule; CD8 molecule; MHC class I antigen; T cell receptor; T lymphocyte; autoantibody; biomarker; cell components; cell mediated lymphocytolysis test; colony stimulating factor; complement; cytolysis; cytotoxic T lymphocyte; graft versus host disease; helper T lymphocyte; hematopoietic stem cells; hypogammaglobulinemia; immunosuppression; interleukin 3; laboratory mouse; systemic lupus erythematosus; thymus

The long-term effects of parent-into-F1 graft-versus-host reaction (GVHR) was investigated by following splenic T cell markers and function for up to 18 months after GVHR induction. Despite the appearance of adequate numbers of T cells which expressed the normal compliment of T lymphocyte markers, these cells still failed to generate MHC self-restricted, CD4-mediated T helper responses. This defect was not due to suppression or a defect in antigen-presenting cell function. Analysis of donor chimerism in parent-into-F1 GVHR indicated three phases of repopulation: an expansion phase of donor T cells; a phase of host cell destruction; and a donor repopulation phase in which extensive donor cell repopulation is observed. Donor T cells that induce GVHR were studied for T cell receptor repertoire by Vbeta analyses. It was observed that donor T cell expressing the Vbeta markers of antihost reactivity were selectively expanded during GVHR. Vbeta analysis was also used to investigate the possible synergy between class I GVHR and donor-antihost m1s recognition. It was found that donor-antihost recognition of class I H-2 and m1s(a) resulted in acute GVHR, and preferential expansion of the Vbeta T cell receptor reactive with m1s(a). Depletion of these Vbeta T cells resulted in reduced donor chimerism, but not in abrogation of GVH-induced immune deficiency.

父级 - into-f1移植物与宿主反应（GVHR）的长期影响 通过遵循脾T细胞标记和功能来研究 GVHR诱导后18个月。尽管有足够的数字 表达T淋巴细胞标记正常称赞的T细胞， 这些细胞仍然无法生成MHC自限制的CD4介导的T 助手响应。该缺陷不是由于抑制或缺陷 抗原呈递细胞功能。分析供体嵌合体 parent-Into-f1 GVHR指示了三个阶段的重生阶段：扩展 供体T细胞的相；宿主细胞破坏的阶段；和捐助者 观察到广泛的供体细胞再捕集的重生阶段。 研究了诱导GVHR的供体T细胞用于T细胞受体库 通过VBETA分析。观察到表达VBETA的供体T细胞 在GVHR期间，选择性扩大了抗抑制反应性的标记。 vbeta 分析还用于研究I类可能的协同作用 GVHR和捐助者antihost M1识别。发现捐助者 - 抗thihost 识别I类H-2和M1S（A）导致急性GVHR，并且 VBETA T细胞受体与M1s的优先扩展（a）。 这些vbeta T细胞的耗竭导致供体嵌合体减少，但 没有废除GVH诱导的免疫缺陷。