Drobyski W R, Piaskowski V, Ash R C, Casper J T, Truitt R L
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Transplantation. 1990 Oct;50(4):625-32. doi: 10.1097/00007890-199010000-00020.
T cell depletion has decreased the incidence and severity of graft-versus-host disease following transplantation of allogeneic bone marrow. In the treatment of leukemia, decreased GVHD has often been associated with diminished antileukemia or graft-versus-leukemia (GVL) reactivity resulting in higher relapse rates. However, we have not seen a loss of the GVL effect following transplantation of marrow grafts depleted of CD3+ T cells. This suggests that non-T-cell effectors may play a role in preventing leukemic relapse. To study whether natural killer and lymphokine-activated killer (LAK) activity in BM was compromised by T cell depletion, the effect of T-cell-specific monoclonal antibodies against CD3 and CD6 determinants alone, or in combination, on the generation and expansion of NK/LAK cells was examined in vitro and compared to the effect of T depletion on mitogen-driven T cell proliferation. Limiting dilution analysis revealed that T depletion with CD3 and/or CD6 specific antibodies significantly reduced the number of proliferating T lymphocytes but did not significantly affect the frequency of cells able to expand and mediate LAK activity. Bone marrow, depleted of CD3+ or CD6+ T cells, generated levels of LAK activity equivalent to non-T-cell-depleted bone marrow following long-term culture in recombinant interleukin 2. CD3- NKH-1+ cells were the predominant population in rIL-2 expanded marrow cultures prior to transplant and in the peripheral blood of patients who had received a CD3-depleted marrow graft 21-65 days earlier. These studies show that it is possible to selectively reduce GVH-reactive T cells in allogeneic bone marrow while retaining non-T-effector cells with potential to mediate an antileukemia effect in vivo.
在异基因骨髓移植后，T细胞清除降低了移植物抗宿主病的发生率和严重程度。在白血病治疗中，移植物抗宿主病的减轻常常与抗白血病或移植物抗白血病（GVL）反应性降低相关，导致更高的复发率。然而，在移植去除CD3 + T细胞的骨髓移植物后，我们并未观察到GVL效应的丧失。这表明非T细胞效应器可能在预防白血病复发中发挥作用。为了研究骨髓中的自然杀伤细胞和淋巴因子激活的杀伤细胞（LAK）活性是否因T细胞清除而受损，我们在体外研究了针对CD3和CD6决定簇的T细胞特异性单克隆抗体单独或联合使用对NK/LAK细胞生成和扩增的影响，并将其与T细胞清除对丝裂原驱动的T细胞增殖的影响进行比较。极限稀释分析显示，用CD3和/或CD6特异性抗体清除T细胞可显著减少增殖T淋巴细胞的数量，但对能够扩增并介导LAK活性的细胞频率没有显著影响。在重组白细胞介素2中长期培养后，去除CD3 +或CD6 + T细胞的骨髓产生的LAK活性水平与未去除T细胞的骨髓相当。在移植前的重组白细胞介素2扩增骨髓培养物以及2l - 65天前接受去除CD3骨髓移植物的患者外周血中，CD3 - NKH - 1 +细胞是主要群体。这些研究表明，在异基因骨髓中选择性减少GVH反应性T细胞的同时保留具有在体内介导抗白血病作用潜力的非T效应细胞是可能的。
