Davenport C, Kumar V, Bennett M
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235.
J Immunol. 1993 Aug 1;151(3):1597-605.
There is current interest in using umbilical cord blood cells as a substitute for bone marrow cells (BMC) in human transplantation. However, T cell-depleted BMC are more susceptible to rejection. Because CBC lack mature T cells, mouse newborn liver cells (NLC) were used as a model to investigate the role of T cells in engraftment. BALB/c BMC, C.B-17 scid/scid (SCID) BMC, and BALB/c NLC were transplanted into lethally irradiated BALB/c and (B6 x DBA/2) F1 (B6D2F1) hosts. Splenic 125IUdR incorporation 5 days later assessed engraftment. BALB/c BMC, NLC, and SCID BMC grew well in BALB/c hosts, but only BALB/c BMC grew in B6D2F1 hosts. This suggests that T cells are necessary for engraftment of H-2d stem cells in the B6D2F1 host. Addition of BALB/c thymocytes to SCID BMC or NLC allowed engraftment in the F1 hosts. It appears that NK cells mediated the resistance because their depletion by mAb increased engraftment of SCID BMC or NLC. Anti-NK1.1 mAb and -asialo GM1 serum eliminate all NK cells, although anti-5E6 mAb eliminate a subpopulation of NK cells that responds to Hh-1d (determinant 2+) stem cells. Treatment of F1 hosts with any of these mAb prevented rejection of SCID BMC or BALB/c NLC. Also, activation of NK cells by poly I:C caused rejection of donor cells in the F1 that could not be overcome by the presence of thymocytes. This effect of the poly I:C could also be reversed by mAb depletion of host NK cells. Thus, engraftment of stem cells is influenced by the presence of donor T cells and the activation level of host NK cells.
目前人们对在人类移植中使用脐带血细胞替代骨髓细胞（BMC）很感兴趣。然而，去除T细胞的BMC更容易被排斥。由于脐带血细胞缺乏成熟T细胞，因此使用新生小鼠肝细胞（NLC）作为模型来研究T细胞在植入中的作用。将BALB/c BMC、C.B-17 scid/scid（SCID）BMC和BALB/c NLC移植到经致死剂量照射的BALB/c和（B6×DBA/2）F1（B6D2F1）宿主中。5天后通过脾细胞125IUdR掺入评估植入情况。BALB/c BMC、NLC和SCID BMC在BALB/c宿主中生长良好，但只有BALB/c BMC在B6D2F1宿主中生长。这表明T细胞对于B6D2F1宿主中H-2d干细胞的植入是必需的。向SCID BMC或NLC中添加BALB/c胸腺细胞可使其在F1宿主中植入。似乎NK细胞介导了这种抗性，因为用单克隆抗体清除NK细胞可增加SCID BMC或NLC的植入。抗NK1.1单克隆抗体和去唾液酸GM1血清可清除所有NK细胞，而抗5E6单克隆抗体可清除对Hh-1d（决定簇2+）干细胞有反应的NK细胞亚群。用这些单克隆抗体中的任何一种处理F1宿主可防止SCID BMC或BALB/c NLC被排斥。此外，聚肌胞苷酸（poly I:C）激活NK细胞会导致F1宿主中的供体细胞被排斥，而胸腺细胞的存在无法克服这种排斥。poly I:C的这种作用也可通过单克隆抗体清除宿主NK细胞来逆转。因此，干细胞的植入受供体T细胞的存在和宿主NK细胞的激活水平影响。
