Wambua P P, Iwabuchi K, Iwabuchi C, Ogasawara K, Itoh Y, Arase H, Kajiwara M, Gotohda T, Kajino K, Good R A
Institute of Immunological Science, Hokkaido University, Japan.
Microbiol Immunol. 1994;38(11):879-90. doi: 10.1111/j.1348-0421.1994.tb02141.x.
Thymocytes which have developed in the C3H thymus showed depressed proliferative responses to stimulation with anti-CD3 antibody as compared with those which have developed in the thymus of other strains of mice (i.e. AKR). The present study was conducted to analyze immunological functions of the thymic stromal cell population (low-density adherent cells, LDAC) in the C3H mice using allogeneic bone marrow (BM) chimeras established by BM transplantation in the reciprocal combination of AKR and C3H mice as donor or recipient. The thymic LDAC from C3H mice or the [AKR(donor)-->C3H(recipient)] chimeras contained a high proportion of Mac-1+ cells as compared to AKR mice or the [C3H-->AKR] chimeras. The proportion of Mac-1+ cells paralleled the IL-1- and PGE2-secreting ability of the LDAC cultured either in the presence or absence of LPS and also paralleled the antigen-presenting cell functions of the LDAC. Furthermore, after anti-CD3 stimulation the PGE2 inhibited more profoundly proliferative responses of [AKR-->C3H] or normal C3H thymocytes than those of the [C3H-->AKR] chimera or normal AKR thymocytes. A PGE2 inhibitor, indomethacin, reversed the depressed responses of the thymocytes which had developed in the C3H thymus. These findings suggest that the lower responsiveness of thymocytes from [AKR-->C3H] chimeras to anti-CD3 stimulation may be attributable to large amounts of PGE2 secreted by LDAC and/or to increased sensitivity of thymocytes themselves to PGE2.
与在其他品系小鼠（如AKR）胸腺中发育的胸腺细胞相比，在C3H胸腺中发育的胸腺细胞对抗CD3抗体刺激的增殖反应受到抑制。本研究旨在利用通过将AKR和C3H小鼠作为供体或受体进行相互组合的骨髓移植建立的同种异体骨髓（BM）嵌合体，分析C3H小鼠胸腺基质细胞群体（低密度贴壁细胞，LDAC）的免疫功能。与AKR小鼠或[C3H→AKR]嵌合体相比，C3H小鼠或[AKR（供体）→C3H（受体）]嵌合体的胸腺LDAC中Mac-1+细胞比例较高。Mac-1+细胞的比例与在有或无LPS情况下培养的LDAC分泌IL-1和PGE2的能力平行，也与LDAC的抗原呈递细胞功能平行。此外，抗CD3刺激后，PGE2对[AKR→C3H]或正常C3H胸腺细胞增殖反应的抑制作用比对[C3H→AKR]嵌合体或正常AKR胸腺细胞的抑制作用更显著。PGE2抑制剂吲哚美辛可逆转在C3H胸腺中发育的胸腺细胞的抑制反应。这些发现表明，[AKR→C3H]嵌合体的胸腺细胞对抗CD3刺激反应性较低可能归因于LDAC分泌的大量PGE2和/或胸腺细胞自身对PGE2敏感性增加。
