Yao Zhengju, Cui Yongzhi, Watford Wendy T, Bream Jay H, Yamaoka Kunihiro, Hissong Bruce D, Li Denise, Durum Scott K, Jiang Qiong, Bhandoola Avinash, Hennighausen Lothar, O'Shea John J
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1000-5. doi: 10.1073/pnas.0507350103. Epub 2006 Jan 17.
Cytokines that use the common gamma chain gammac are critical for lymphoid development and function. Mutations of the IL-7 receptor, gammac, or its associated kinase, Jak3, are the major cause of human severe combined immunodeficiency. Although activated by IL-7, Stat5a/b (Stat, signal transducer and activator of transcription) have been thought to play limited roles in lymphoid development. However, we now show that mice completely deficient in Stat5a/b have severely impaired lymphoid development and differentiation. Absence of Stat5 also abrogates T cell receptor gamma rearrangement and survival of peripheral CD8(+) T cells. Thus, deficiency of Stat5 results in severe combined immunodeficiency, similar in many respects to deficiency of IL-7R, gammac, and Jak3.
利用共同γ链（γc）的细胞因子对淋巴细胞发育和功能至关重要。白细胞介素7受体（IL-7受体）、γc或其相关激酶Jak3的突变是人类严重联合免疫缺陷的主要原因。尽管Stat5a/b（Stat，信号转导及转录激活因子）被白细胞介素7激活，但一直被认为在淋巴细胞发育中作用有限。然而，我们现在发现，完全缺乏Stat5a/b的小鼠淋巴细胞发育和分化严重受损。Stat5缺失还会消除T细胞受体γ重排以及外周CD8(+) T细胞的存活。因此，Stat5缺陷导致严重联合免疫缺陷，在许多方面与IL-7R、γc和Jak3缺陷相似。
