Ogimoto M, Yoshikai Y, Matsuzaki G, Ohga S, Matsumoto K, Nomoto K
Department of Immunology, Kyushu University, Fukuoka, Japan.
Immunology. 1990 Mar;69(3):482-6.
Clonal deletion of T cells capable of recognizing both host-type Mls and donor-type Mls occurred in the peripheral mature T-cell pool in radiation bone marrow chimeras of two H-2-compatible Mls-disparate strain combinations of AKR/J(H-2k,Thy-1.1,Mls-1a) and C3H/He(H-2k,Thy-1.2,Mls-1b). In order to determine further the stage at which the clonal deletion occurs in thymus, we examined the kinetics of thymocytes bearing V beta 6 capable of recognizing Mls-1a in both C3H/He----AKR/J and AKR/J----C3H/He chimeras. An almost complete replacement from host-derived cells to donor-derived cells occurred by Day 21 after reconstitution in both chimeras. At this stage, CD4+CD8+ double-positive thymocytes contained an appreciable number of cells that expressed V beta 6 on their surface, albeit at low intensity, whereas CD4 or CD8 single-positive thymocytes which expressed a high density of V beta 6 were virtually abolished in both C3H----AKR and AKR----C3H chimeras on Day 21. These results suggest that clonal deletion of self-Mls-reactive T cells begins at an early stage when the thymocytes interact with the early appearing donor-derived haemotopoietic cells and relatively radio-resistant host-derived cells in thymus of radiation bone marrow chimeras.
在AKR/J(H-2k,Thy-1.1,Mls-1a)和C3H/He(H-2k,Thy-1.2,Mls-1b)这两种H-2兼容但Mls不同的品系组合的辐射骨髓嵌合体的外周成熟T细胞库中,能够识别宿主型Mls和供体型Mls的T细胞发生了克隆性缺失。为了进一步确定胸腺中克隆性缺失发生的阶段,我们检测了在C3H/He→AKR/J和AKR/J→C3H/He嵌合体中能够识别Mls-1a的携带Vβ6的胸腺细胞的动力学变化。在两种嵌合体重建后第21天,宿主来源的细胞几乎完全被供体来源的细胞所取代。在此阶段,CD4+CD8+双阳性胸腺细胞含有相当数量表面表达Vβ6的细胞,尽管表达强度较低,而在第21天,在C3H→AKR和AKR→C3H嵌合体中,表达高密度Vβ6的CD4或CD8单阳性胸腺细胞实际上已被消除。这些结果表明,自身Mls反应性T细胞的克隆性缺失始于早期阶段,此时胸腺细胞与辐射骨髓嵌合体胸腺中早期出现的供体来源造血细胞和相对抗辐射的宿主来源细胞相互作用。