A CD8/Lck transgene is able to drive thymocyte differentiation

J Immunol. 2006 Nov 1;177(9):6007-17. doi: 10.4049/jimmunol.177.9.6007.

Abstract

Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8alpha-associated Lck in driving CD8 single positive (SP) thymocyte development. We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8alpha fused to full-length Lck. In mice deficient for CD8alpha and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8alpha. A CD8alpha/Lck kinase-dead chimera also resulted in reconstitution of CD8 SP thymocytes. Our results suggest that CD8alpha-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CD8 SP development may not necessarily depend on Lck kinase activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8 Antigens / analysis
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism*
  • Cell Differentiation* / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology*
  • Transgenes

Substances

  • CD8 Antigens
  • CD8alpha antigen
  • Recombinant Fusion Proteins
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)