Premium
Interferon‐regulatory factors during development of CD4 and CD8 thymocytes
Author(s) -
SIMON A. K.,
DESROIS M.,
SCHMITTVERHULST A.M.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00271.x
Subject(s) - biology , cd8 , thymocyte , irf1 , mhc class i , cytotoxic t cell , major histocompatibility complex , microbiology and biotechnology , t cell receptor , antigen , transcription factor , t cell , immunology , immune system , gene , genetics , in vitro
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). Toevaluate 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.