Long-Term Survival But Impaired Homeostatic Proliferation of Naïve T Cells in the Absence of p56 lck

• DOI: 10.1126/science.290.5489.127
• Publication Date: 2002-07-27T09:53:24Z
• Authors: Benedict Seddon; Giuseppe Legname; Peter Tomlinson; Rose Zamoyska
• Keywords: CD4-Positive T-Lymphocytes; Mice, Knockout; CD3 Complex; Cell Survival; Lymphoid Tissue; Receptors, Antigen, T-Cell; Gene Expression; Mice, Transgenic; CD8-Positive T-Lymphocytes; Lymphocyte Activation; Mice; 03 medical and health sciences; 0302 clinical medicine; Proto-Oncogene Proteins c-bcl-2; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Doxycycline; Lymphocyte Transfusion; Animals; Homeostasis; Lymphocyte Count; Phosphorylation; Cell Division

Interactions between the T cell receptor (TCR) and major histocompatibility complex antigens are essential for the survival and homeostasis of peripheral T lymphocytes. However, little is known about the TCR signaling events that result from these interactions. The peripheral T cell pool of p56 lck (lck)–deficient mice was reconstituted by the expression of an inducible lck transgene. Continued survival of peripheral naı̈ve T cells was observed for long periods after switching off the transgene. Adoptive transfer of T cells from these mice into T lymphopoienic hosts confirmed that T cell survival was independent of lck but revealed its essential role in TCR-driven homeostatic proliferation of naı̈ve T cells in response to the T cell–deficient host environment. These data suggest that survival and homeostatic expansion depend on different signals.