Eto M, Mayumi H, Tomita Y, Yoshikai Y, Nishimura Y, Maeda T, Ando T, Nomoto K
Department of Immunology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Immunol. 1991 Mar 1;146(5):1402-9.
In cyclophosphamide (CP)-induced tolerance, a long lasting skin allograft tolerance was established in many H-2-identical strain combinations without graft vs host disease. Destruction of donor-reactive T cells of host origin, followed by intrathymic clonal deletion of these cells, has been revealed to be the chief mechanisms of this system. Here, we studied the fate of host-reactive populations in donor-derived T cells of C3H/He (C3H) (H-2k, Mls-1b, Mls-2a) mice rendered CP-induced tolerant to AKR/J (AKR) (H-2k, Mls-1a, Mls-2b), by assessing AKR-derived Thy-1.1+ T cells bearing TCR V beta 3 that are specifically reactive with Mls-2a-encoded Ag of the recipient C3H mice. In the AKR-derived Thy-1.1+ lymph node cells of the C3H mice that had been treated with AKR spleen cells plus CP, CD4(+)-V beta 3+ T cells were obviously decreased by day 10 after the CP treatment. At this stage, the Thy-1.1+ T cells were not detected in the C3H thymus, suggesting that the obvious decrease of CD4(+)-V beta 3+ T cells of AKR origin was not due to intrathymic clonal deletion in the recipient C3H mice. Therefore, the destruction of the host-reactive mature T cells of donor origin, as well as that of the donor-reactive mature T cells of host origin, occurred by the CP treatment at the induction phase. Furthermore, after the establishment of intrathymic mixed chimerism in the recipient C3H mice, V beta 3+ T cells were not detected among the Thy-1.1+ T cells of AKR origin in the mixed chimeric thymus, suggesting that the host-reactive immature T cells repopulated from the injected donor hematopoietic cells were clonally deleted in the recipient thymus. These two mechanisms appear to prevent graft vs host disease in CP-induced tolerance.
在环磷酰胺（CP）诱导的耐受中，在许多H-2相同的品系组合中建立了持久的皮肤同种异体移植耐受，且无移植物抗宿主病。已发现宿主来源的供体反应性T细胞的破坏，随后这些细胞在胸腺内的克隆性缺失，是该系统的主要机制。在此，我们通过评估携带TCR Vβ3的AKR来源的Thy-1.1+ T细胞来研究C3H/He（C3H）（H-2k，Mls-1b，Mls-2a）小鼠在CP诱导下对AKR/J（AKR）（H-2k，Mls-1a，Mls-2b）产生耐受后，宿主反应性群体在供体来源T细胞中的命运，这些T细胞与受体C3H小鼠的Mls-2a编码抗原具有特异性反应。在用AKR脾细胞加CP处理的C3H小鼠的AKR来源的Thy-1.1+淋巴结细胞中，CP处理后第10天，CD4(+)-Vβ3+ T细胞明显减少。在此阶段，在C3H胸腺中未检测到Thy-1.1+ T细胞，这表明AKR来源的CD4(+)-Vβ3+ T细胞的明显减少不是由于受体C3H小鼠胸腺内的克隆性缺失。因此，在诱导阶段，CP处理导致了供体来源的宿主反应性成熟T细胞以及宿主来源的供体反应性成熟T细胞的破坏。此外，在受体C3H小鼠建立胸腺内混合嵌合体后，在混合嵌合胸腺中AKR来源的Thy-1.1+ T细胞中未检测到Vβ3+ T细胞，这表明从注射的供体造血细胞重新填充的宿主反应性未成熟T细胞在受体胸腺中被克隆性删除。这两种机制似乎可预防CP诱导的耐受中的移植物抗宿主病。
