Morshed Sufi Reza M, Mannoor Kaiissar, Halder Ramesh C, Kawamura Hiroki, Bannai Makoto, Sekikawa Hiroho, Watanabe Hisami, Abo Toru
Department of Immunology, Niigata University School of Medicine, Japan.
Eur J Immunol. 2002 Sep;32(9):2551-61. doi: 10.1002/1521-4141(200209)32:9<2551::AID-IMMU2551>3.0.CO;2-C.
Natural killer T (NKT) cells and CD5(+)B cells were searched for in various immune organs of autoimmune prone (NZBxNZW)F(1) (NZB/W F(1)) mice. The number of lymphocytes increased in the liver, spleen, and peritoneal cavity after the onset of disease (at the age of 30 weeks) while the number of thymocytes decreased at that time. Prominent changes of lymphocyte subsets were seen in the liver and peritoneal cavity, namely, expansion of IL-2Rbeta(+)TCRalpha beta(int) cells in the liver and of CD5(+)B220(+) cells in the peritoneal cavity. The majority of TCRalpha beta(int) cells in the liver were NK1.1(+), and CD5(+)B cells in the peritoneal cavity were CD1d(+). Proteinuria became prominent in NZB/W F(1) mice with the progression of disease. In parallel with this progression, the proportion of NKT cells decreased slightly in the liver, but their absolute number remained at a high level in this organ. These NKT cells were CD4(+) and used an invariant chain of Valpha14Jalpha281 for TCRalpha. Reflecting the elevation of CD5(+)B cells, autoantibodies against hepatocyte cytoplasmand denatured DNA were detected in sera. Although NKT cells are known to be immunoregulatory cells in some autoimmune mice, the present results raise the possibility that NKT cells as well as CD5(+)B cells might be associated with the onset of autoimmune diseases in NZB/W F(1) mice. Indeed, NKT cells in F(1) mice had a high potential to induce autoimmune-like inflammationwhen alpha-galactosylceramide was administered or when active NKT cells were transferred into young F(1) mice.
在自身免疫易感的（NZBxNZW）F1（NZB/W F1）小鼠的各种免疫器官中搜索自然杀伤T（NKT）细胞和CD5（+）B细胞。疾病发作后（30周龄时），肝脏、脾脏和腹腔中的淋巴细胞数量增加，而此时胸腺细胞数量减少。在肝脏和腹腔中观察到淋巴细胞亚群的显著变化，即肝脏中IL-2Rβ（+）TCRαβ（int）细胞和腹腔中CD5（+）B220（+）细胞的扩增。肝脏中大多数TCRαβ（int）细胞是NK1.1（+），腹腔中的CD5（+）B细胞是CD1d（+）。随着疾病进展，NZB/W F1小鼠的蛋白尿变得明显。与此进展并行的是，肝脏中NKT细胞的比例略有下降，但其绝对数量在该器官中仍保持在较高水平。这些NKT细胞是CD4（+），并使用Valpha14Jalpha281的恒定链作为TCRα。反映CD5（+）B细胞的升高，在血清中检测到针对肝细胞胞质和变性DNA的自身抗体。尽管已知NKT细胞在一些自身免疫小鼠中是免疫调节细胞，但目前的结果增加了NKT细胞以及CD5（+）B细胞可能与NZB/W F1小鼠自身免疫疾病发病有关的可能性。事实上，当给予α-半乳糖神经酰胺或当活性NKT细胞转移到年轻的F1小鼠中时，F1小鼠中的NKT细胞具有诱导自身免疫样炎症的高潜力。
