Interferon-regulatory factors during development of CD4 and CD8 thymocytes.
Selection events in the thymus occur at the double-positive CD4+ CD8+ (DP) developmental stage leading either to further differentiation of the CD4+ and CD8+ lineages or to deletion. The interferon-regulatory factor IRF-1 has been implicated in signalling for T-cell death and also in CD8+ thymic differentiation. IRF-1 is an activator and IRF-2 a repressor of gene transcription regulated by type 1 interferons (IFN). To evaluate the role of IRF-1 and IRF-2 in the differentiation of CD4 and CD8 thymocytes, we analysed their DNA-binding activity before and after antigenic stimulation at different stages of thymic development and in peripheral T cells. Unseparated, double-positive and single-positive thymocytes as well as peripheral T lymphocytes from mice transgenic (tg) for a T-cell receptor (TCR), restricted either by major histocompatibility complex class I or class II, were stimulated by their nominal antigen. Our results demonstrate that the DNA-binding activity of IRF-2 and, weakly, that of IRF-1 are inducible in total thymocytes in response to antigen. There is no induction of IRF-1/IRF-2 binding activity at the double-positive stage of thymic development in the MHC class II-restricted model whereas in the MHC class I-restricted model IRF-1/IRF-2 activity is induced weakly. At the single-positive stage, antigen induces the IRF-1/IRF-2 DNA binding in both CD4+ and CD8+ thymocytes, but not in mature lymphocytes from the periphery. This pattern of expression suggests that IRF-1/IRF-2 binding activities resulting from antigen stimulation are developmentally regulated. No evidence for a selective role of IRF-1 in the development of the CD8+ lineage was found, however.
Simon
A K
AK
Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, France.
Desrois
M
M
Schmitt-Verhulst
A M
AM
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors