title: A CD8/Lck transgene is able to drive thymocyte differentiation.
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.
authors.affiliation: Dana-Farber Cancer Institute, Department of Pediatric Oncology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Fragoso
authors.forename: Saiju
authors.initials: S
authors.lastname: Pyarajan
authors.forename: Hanna Yoko
authors.initials: HY
authors.lastname: Irie
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burakoff
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019076:Transgenes
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D011993:Recombinant Fusion Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)