Premium
Interleukin‐7 inhibits pre‐T‐cell differentiation induced by the pre‐T‐cell receptor signal and the effect is mimicked by hGM‐CSF in hGM‐CSF receptor transgenic mice
Author(s) -
Yasuda Yuko,
Kaneko Azusa,
Nishijima Ichiko,
Miyatake Shoichiro,
Arai Kenichi
Publication year - 2002
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.1365-2567.2002.01402.x
Subject(s) - biology , t cell receptor , cd8 , receptor , t cell , microbiology and biotechnology , cytotoxic t cell , cellular differentiation , cd3 , signal transduction , immunology , immune system , gene , biochemistry , in vitro
Summary We have previously reported that human granulocyte–macrophage colony‐stimulating factor (hGM‐CSF) causes a stage‐specific inhibition of T‐cell receptor (TCR) αβ cell development in the thymus of transgenic mice constitutively expressing the hGM‐CSF receptor. Since it has been reported that the addition of interleukin‐7 (IL‐7) to fetal thymic organ culture (FTOC) has similar effects, we compared the effects of IL‐7 and hGM‐CSF on TCRαβ cell development in hGM‐CSF receptor transgenic mice. We reconstituted fetal lobes with sorted pre‐T, or post pre‐T CD4 − CD8 − precursor cells. The addition of either IL‐7 or hGM‐CSF to these cultures suppressed further differentiation of pre‐T cells but not post pre‐T cells. At the same time, the cell number was increased, suggesting that pre‐T‐cell proliferation is stimulated by these cytokines. Furthermore, the differentiation of recombination‐activating gene‐1 (RAG‐1)‐deficient pre‐T cells in response to anti‐CD3 antibody stimulation was suppressed by either IL‐7 or hGM‐CSF, suggesting that these cytokines inhibit the pre‐T‐cell receptor (pre‐TCR) signal. This inhibition is unexpected because the pre‐TCR signal and the IL‐7 signal have previously been considered to be co‐operative. Recent analysis of the downstream events of IL‐7 receptor and GM‐CSF receptor revealed that they share common signal transduction molecules. Our results show that IL‐7 is able to promote pre‐T cell proliferation and to suppress differentiation induced by the pre‐TCR signal. GM‐CSF can mimic these biological activities of IL‐7 when the pre‐T cells express GM‐CSF receptors. Our data suggest that both timing and level of activation of the IL‐7 signalling pathway must be precisely regulated to facilitate the differentiation of thymocytes.