Interferon-regulatory factors during development of CD4 and CD8 thymocytes

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Item Type:	Article
Title:	Interferon-regulatory factors during development of CD4 and CD8 thymocytes
Creators Name:	Simon, A.K., Desrois, M. and Schmitt-Verhulst, A.M.
Abstract:	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.
Keywords:	Antigens, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Culture Techniques, Cell Differentiation, DNA-Binding Proteins, Interferon Regulatory Factor-1, Interferon Regulatory Factor-2, Transgenic Mice, Phosphoproteins, Repressor Proteins, Thymus Gland, Transcription Factors, Transcription Factors / Metabolism, Animals, Mice
Source:	Immunology
ISSN:	0019-2805
Publisher:	Blackwell Publishing
Volume:	91
Number:	3
Page Range:	340-5
Date:	July 1997
Official Publication:	https://doi.org/10.1046/j.1365-2567.1997.00271.x
PubMed:	View item in PubMed

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