β-Selection of immature thymocytes is less dependent on CD45 tyrosinephosphatase

Abstract

Tyrosine kinase p56(lck) plays a pivotal role in β-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 p56(lck) 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 p56(lck) 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 β-selection due to the expression of functionally rearranged TCR-β on CD25+ DN thymocytes. However, CD25+ thymocytes increased in DN stage when TCR-Tg were backcrossed with p56(lck) 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 p56(lck) deficient but not in CD45 deficient mice. This suggests that CD45 is dispensable for β-selection though p56(lck) is required.