TCR and IL-7 receptor signals can operate independently or synergize to promote lymphopenia-induced expansion of naive T cells.
TCR and cytokine signals induce naive T cells to undergo spontaneous divisions as part of a homeostatic response to conditions of T cell deficiency. The conditions under which these signals evoke the homeostatic response and their interaction with each other are poorly understood, and yet are very important clinically in considering strategies for immune reconstitution. Here, we show that p56(lck) (lck)-mediated TCR signals and IL-7R signals are each able to stimulate T cell proliferation in lymphopenic hosts independently of one another, but can also synergize to facilitate proliferation. Furthermore, the relative contribution to the homeostatic response by TCR and cytokine signals is not fixed and critically depends on both the degree of lymphopenia and specific characteristics of individual T cell clones. Finally, we show that only lck and not fyn can mediate the TCR-driven proliferation, while neither lck nor fyn is required for IL-7R-induced proliferation.
Seddon
Benedict
B
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
Zamoyska
Rose
R
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D004357:Drug Synergism; D016654:Genes, RAG-1 / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000235:genetics; D008231:Lymphopenia / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
D000276:Adjuvants, Immunologic; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn