title: Control of recent thymic emigrant survival by positive selection signals and early growth response gene 1.
abstract: Early growth response gene 1 (Egr1) is a transcriptional regulator whose expression can be induced by multiple signals including the TCR. Egr1 has been shown to promote positive selection, but an investigation of its role in T cell homeostasis has not been reported. The possibility that similar signals control both positive selection and peripheral T cell homeostasis led us to investigate the role of Egr1 in the maintenance of peripheral T cells. We have found that on TCR transgenic backgrounds, Egr1-deficient mice have a reduction in their number of naive T cells. Although Egr1-deficient animals have a low percentage of mature thymocytes due to inefficient positive selection, the absolute number of mature thymocytes is only slightly reduced due to increased thymus size in Egr1-deficient mice. Despite possessing near normal numbers of mature thymocytes, we find that Egr1-deficient mice have poor accumulation of recent thymic emigrants (RTE) in the periphery. The poor accumulation of RTE in Egr1-deficient mice appears to originate from decreased survival of mature thymocytes and RTE, which we have observed both in vitro and in vivo. These findings suggest that an Egr1-mediated signal during positive selection promotes not only the production of single positive thymocytes, but also the survival of selected thymocytes until they can become established in the periphery.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Schnell
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Kersh
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D051766:Early Growth Response Protein 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D011948:Receptors, Antigen, T-Cell