T CELL FUNCTION IN T CELL DEPLETED BONE MARROW TRANSPLANTATION

从骨髓中消除T细胞在同种异体移植中都是令人感兴趣的。 自体骨髓移植- -作为一种防止移植物 同种异体骨髓移植中的抗宿主病， 消除或清除表达T细胞表面标志物的恶性细胞 自体骨髓移植治疗T细胞肿瘤 移植我们开发了一种方法， 恶性T细胞骨髓群体的骨髓;这些方法是 然后用于临床方案，评估使用 同种异体HLA错配、T细胞耗竭骨髓和自体骨髓 清除恶性T细胞治疗侵袭性 造血系统恶性肿瘤恒河猴临床前研究 证明了CD 4 + T细胞重建和体内T细胞的发育， 细胞免疫活性与输注的T细胞数量相关。 骨髓中残留的T细胞可能是输注的T细胞 细胞耗尽的骨髓在随后的产生中发挥了核心作用。 T细胞群体。这一结论已在小鼠研究中得到证实 其中已经鉴定了三个T细胞祖细胞库， 有助于骨髓移植后最终的T细胞再增殖。 这些再生的T细胞群的功能能力也是 感兴趣人辅助性T细胞对外源性MHC编码抗原的应答 已经研究了通过刺激鼠细胞群表达的抗原 并发现其在评估人类T辅助细胞中具有特殊用途 函数，因为此主要响应需要重新处理 刺激鼠抗原和与人类相关的呈递 II基因产物。鼠抗原再加工的要求， 通过应答型细胞呈递（而不是鼠刺激的 细胞）被发现是由于缺乏鼠抗原呈递 细胞活化和应答T细胞活化。

The elimination of T cells from marrow is of interest both in allogeneic and autologous marrow transplantation - - as a means of preventing graft versus host disease in allogeneic marrow transplantation and as a means of eliminating or purging malignant cells expressing T cell surface markers from marrow in treating T cell neoplasms by autologous marrow transplantation. We developed approaches for depleting normal and malignant T cell marrow populations from marrow; these approaches were then used in clinical protocols assessing the feasibility of utilizing allogenic HLA-mismatched, T cell depleted marrow and autologous marrow purged of malignant T cells in the treatment of aggressive hematolymphopoietic malignancies. Preclinical studies in rhesus monkeys demonstrated that CD4+ T cell reconstitution and development of in vivo T cell immunocompetence correlated with the number of T cells infused in the marrow raising the possibility that residual T cells in the infused T cell-depleted marrow played a central role in the generation of subsequent T cell populations. This conclusion has been confirmed in murine studies in which three T cell progenitor pools have been identified which contribute to final T cell repopulation following marrow transplantation. The functional capacities of these regenerated T cell populations is also of interest. The human T helper cell response to xenogenic MHC encoded antigens expressed by stimulating murine cell populations has been studied and found to be of special use in the assessment of human T helper cell function in that this primary response requires reprocessing of the stimulating murine antigens and presention in association with human Class II gene products. The requirement for reprocessing of murine antigen and presentation by responder-type cells (rather than murine stimulating cells) was found to be due to a lack both of murine antigen presenting cell activation and responder T cell activation.