Yuuki H, Yoshikai Y, Kishihara K, Iwasaki A, Matsuzaki G, Takimoto H, Nomoto K
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Eur J Immunol. 1990 Jul;20(7):1475-82. doi: 10.1002/eji.1830200711.
Although T cells proliferate and differentiate primarily in the thymus, athymic nude mice contain an appreciable level of T cell receptor alpha/beta and gamma/delta T cells, suggesting the existence of the extrathymic pathway in the development of both T cells. Recent studies with nude mice indicate that clonal deletion of self-reactive T cells does not occur extrathymically. In the present study, we have investigated the responsiveness of self-reactive T cells differentiating along an extrathymic pathway in aged BALB/c (H-2d, Mls-1b2a, I-E+, 7-8 month old) nude mice. Consistent with recent reports, T cells bearing V beta 3 or V beta 11, which are important for recognizing proteins encoded by the Mls-2a or the I-E allele, respectively, are readily detected in age nude mice. The V beta 3- or V beta 11-bearing T cells, however, do not proliferate in response to staphylococcal enterotoxin A which specifically stimulates V beta 3- or V beta 11-bearing T cells. When exogenous recombinant interleukin 2 was added to the culture, the V beta 3-bearing T cells in aged nude mice significantly proliferated in response to staphylococcal enterotoxin A. Aged nude mice also contained a substantial level of gamma/delta T cells which account for 15.6% of all Thy-1.2+ cells. The gamma/delta T cells proliferated and produced a significant level of interleukin 2 in response to the 65-kDa mycobacterial heat-shock protein, which is highly homologous to its eukaryotic counterpart. These results suggest that unresponsiveness of self-reactive T cells may be reversed by T cells responding to stress proteins expressed by the invading microbes and/or the stressed autologous cells.
尽管T细胞主要在胸腺中增殖和分化，但无胸腺裸鼠体内仍含有相当数量的T细胞受体α/β和γ/δ T细胞，这表明两种T细胞的发育都存在胸腺外途径。最近对裸鼠的研究表明，自身反应性T细胞的克隆清除在胸腺外不会发生。在本研究中，我们调查了在老龄BALB/c（H-2d，Mls-1b2a，I-E+，7-8月龄）裸鼠中沿胸腺外途径分化的自身反应性T细胞的反应性。与最近的报道一致，分别对识别由Mls-2a或I-E等位基因编码的蛋白质很重要的携带Vβ3或Vβ11的T细胞，在老龄裸鼠中很容易被检测到。然而，携带Vβ3或Vβ11的T细胞对特异性刺激携带Vβ3或Vβ11的T细胞的葡萄球菌肠毒素A没有增殖反应。当向培养物中添加外源性重组白细胞介素2时，老龄裸鼠中携带Vβ3的T细胞对葡萄球菌肠毒素A有显著增殖反应。老龄裸鼠还含有大量的γ/δ T细胞，占所有Thy-1.2+细胞的15.6%。γ/δ T细胞对与真核对应物高度同源的65-kDa分枝杆菌热休克蛋白有增殖反应，并产生大量的白细胞介素2。这些结果表明，自身反应性T细胞的无反应性可能会被对入侵微生物和/或应激自体细胞表达的应激蛋白作出反应的T细胞所逆转。
