Beta-selection of immature thymocytes is less dependent on CD45 tyrosinephosphatase.
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.
Sato
T
T
Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Kishihara
K
K
Mak
T W
TW
Habu
S
S
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018960:Hyaluronan Receptors / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; C064655:V(D)J recombination activating protein 2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens