Tsukahara A, Kawamura H, Iiai T, Moroda T, Suzuki S, Tada T, Minagawa M, Musha N, Hatakeyama K, Abo T
Department of Immunology, Niigata University School of Medicine, Niigata, Japan.
Microbiol Immunol. 1998;42(6):447-56. doi: 10.1111/j.1348-0421.1998.tb02308.x.
When C57BL/6 (B6) mice were irradiated (9 Gy) and received bone marrow (BM) cells of B6-lpr/lpr mouse origin (i.e., lpr-->B6), all mice died within 6 days. In the irradiated B6 mice, radioresistant CD3 IL-2Rbeta+ NK cells and IL-2Rbeta+ CD3int cells (i.e., CD3int cells of extrathymic origin) remained, especially in the liver. There were two subsets, NK1.1+ and NK1.1-, among the IL-2Rbeta+ CD3int cells. However, the NK1.1+ subset (i.e., NK1.1- T cells) was much more radioresistant, and the majority of CD3int cells belonged to this subset in irradiated mice. The expansion of lymphocytes from injected BM cells did not occur in the irradiated B6 mice. However, such expansion did take place in irradiated B6-lpr/lpr mice injected with both BM cells of B6-lpr/lpr and B6 origin. As a result, the mice subjected to BM cells survived. Irradiated B6 mice were treated in vivo with anti-NK1.1 mAb or anti-asialoGM1 antibody to eliminate NK cells alone or both NK cells and NK1.1+ T cells. When irradiated B6 mice were pretreated with anti-NK1.1 mAb, the mice could survive. These results suggest that intact NK1.1+ T cells of extrathymic origin may recognize abnormal BM cells with the lpr gene and inhibit the expansion of lymphocytes, including abnormal double-negative CD4 8 cells, in B6-lpr/lpr mice. To inhibit the expansion of lymphocytes, mechanisms other than Fas ligand/Fas molecules on extrathymic T cells may be responsible.
当C57BL/6(B6)小鼠接受9 Gy照射并输入源自B6-lpr/lpr小鼠的骨髓(BM)细胞(即lpr→B6)时,所有小鼠均在6天内死亡。在接受照射的B6小鼠中,具有辐射抗性的CD3 IL-2Rβ⁺ NK细胞和IL-2Rβ⁺ CD3int细胞(即胸腺外起源的CD3int细胞)依然存在,尤其是在肝脏中。在IL-2Rβ⁺ CD3int细胞中有NK1.1⁺和NK1.1⁻两个亚群。然而,NK1.1⁺亚群(即NK1.1⁻ T细胞)的辐射抗性更强,在受照射小鼠中,大多数CD3int细胞属于该亚群。注入的BM细胞来源的淋巴细胞在受照射的B6小鼠中未发生增殖。然而,在同时注入源自B6-lpr/lpr和B6的BM细胞的受照射B6-lpr/lpr小鼠中,这种增殖确实发生了。结果,接受BM细胞的小鼠存活了下来。对受照射的B6小鼠进行体内抗NK1.1单克隆抗体或抗去唾液酸GM1抗体处理,以单独清除NK细胞或同时清除NK细胞和NK1.1⁺ T细胞。当用抗NK1.1单克隆抗体预处理受照射的B6小鼠时,这些小鼠能够存活。这些结果表明,胸腺外起源的完整NK1.1⁺ T细胞可能识别携带lpr基因的异常BM细胞,并抑制B6-lpr/lpr小鼠中包括异常双阴性CD4 8细胞在内的淋巴细胞增殖。为抑制淋巴细胞增殖,胸腺外T细胞上除Fas配体/Fas分子以外的机制可能起作用。