Sato T, Kishihara K, Mak T W, Habu S
Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Immunol Lett. 1998 Dec;64(2-3):133-8. doi: 10.1016/s0165-2478(98)00094-7.
Tyrosine kinase p56lck plays a pivotal role in beta-selection from CD4-8- (DN) to CD4+8+ (DP) developing pathway, but it is unclear how CD45 transmembrane tyrosinephosphatase is involved in this process although CD45 activates p56lck by dephosphorylating its tyrosine-505. To analyze this issue, we produced double mutant mice of T-cell receptor transgenic mice (TCR-Tg) or RAG-2 knock out mice backcrossed with either p56lck or CD45 knock out mice. In TCR-Tg, CD25+DN thymocytes almost disappeared and CD25-44-DN cells of further developing stage increased, implying that all DN thymocytes can undergo beta-selection due to the expression of functionally rearranged TCR-beta on CD25+ DN thymocytes. However, CD25+ thymocytes increased in DN stage when TCR-Tg were backcrossed with p56lck deficient mice but not with CD45 deficient mice. Similarly, DP thymocyte induction with CD25+ cell reduction in RAG-2 knock out mice by injection of anti-CD3 mAb was inhibited in p56lck deficient but not in CD45 deficient mice. This suggests that CD45 is dispensable for beta-selection though p56lck is required.
酪氨酸激酶p56lck在从CD4-8-（双阴性，DN）到CD4+8+（双阳性，DP）的发育途径的β选择中起关键作用，但尽管CD45通过使其酪氨酸-505去磷酸化来激活p56lck，目前尚不清楚CD45跨膜酪氨酸磷酸酶是如何参与这一过程的。为了分析这个问题，我们培育了与p56lck或CD45基因敲除小鼠回交的T细胞受体转基因小鼠（TCR-Tg）或RAG-2基因敲除小鼠的双突变小鼠。在TCR-Tg小鼠中，CD25+DN胸腺细胞几乎消失，而处于进一步发育阶段的CD25-44-DN细胞增加，这意味着所有DN胸腺细胞都可以由于CD25+DN胸腺细胞上功能性重排的TCR-β的表达而经历β选择。然而，当TCR-Tg与p56lck缺陷小鼠而不是CD45缺陷小鼠回交时，DN阶段的CD25+胸腺细胞增加。同样，通过注射抗CD3单克隆抗体在RAG-2基因敲除小鼠中诱导的DP胸腺细胞减少，在p56lck缺陷小鼠中受到抑制，而在CD45缺陷小鼠中则不受抑制。这表明，尽管p56lck是必需的，但CD45对于β选择是可有可无的。
