Impaired generation of CD8+ thymocytes in Ets-1-deficient mice.
The Ets family of transcription factors function as key regulators of multiple aspects of immune cell development and function. To date, Ets-1 has been implicated in regulating early stages of thymic maturation and lymphocyte function and homeostasis. This report describes a novel role for Ets-1 in supporting later stages of thymic selection, in that positive selection of MHC class I-restricted CD4+CD8+ double-positive thymocytes is markedly inhibited in mice expressing a hypomorphic allele of Ets-1. This effect is thymocyte intrinsic, as Ets-1 mutant thymocytes fail to efficiently generate CD8+ single-positive thymocytes in mixed bone marrow chimeric backgrounds. Although peripheral CD8+ T cells are present in Ets-1 mutant mice, both CD4+ and CD8+ subsets contain an elevated proportion of cells with an effector memory (CD62L-CD44+) phenotype. In addition, while thymic expression of Thy1 is relatively normal, peripheral T cells isolated from Ets-1 mutant mice display a striking loss of Thy1 expression. These data identify Ets-1 as a key transcription factor regulating thymocyte positive selection and lineage commitment of MHC class I-restricted thymocytes.
Clements
James L
JL
Department of Immunology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA. james.clements@roswellpark.org
John
Shinu A
SA
Garrett-Sinha
Lee Ann
LA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D005260:Female; D006182:H-Y Antigen / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050784:Proto-Oncogene Protein c-ets-1 / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
C494042:Ets1 protein, mouse; D006182:H-Y Antigen; D050784:Proto-Oncogene Protein c-ets-1; D014157:Transcription Factors