Positive and Negative Selection of Thymocytes Depends on Lck Interaction with the CD4 and CD8 Coreceptors

• Published in: The Journal of immunology (1950) 2001-01, Vol.166 (2), p.809-818
• Main Authors: Trobridge, Patty A, Forbush, Katherine A, Levin, Steven D
• Format: Article
• Language: English
• Subjects: Animals; CD4 antigen; CD4 Antigens - biosynthesis; CD4 Antigens - metabolism; CD8 antigen; CD8 Antigens - biosynthesis; CD8 Antigens - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Lck protein; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - deficiency; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thymus Gland - cytology; Thymus Gland - enzymology; Thymus Gland - immunology; Thymus Gland - metabolism; Transgenes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.2.809

Considerable evidence supports a role for the Src family protein tyrosine kinase Lck in regulating multiple aspects of thymocyte development. In this report, we establish that early events in T lymphopoiesis are restored to Lck-deficient mice by provision of a transgene encoding a version of Lck that cannot interact with the coreceptors CD4 and CD8. In addition, we demonstrate that later events in thymocyte development, specifically, the processes of positive and negative selection, are compromised in mice where the only Lck available cannot associate with either CD4 or CD8. We conclude that not only is Lck activity required for positive and negative selection, but that that activity must be coupled to the CD4 and CD8 coreceptors.