Enhanced TCR-induced apoptosis in interferon regulatory factor 4-deficient CD4(+) Th cells

The Journal of Experimental Medicine
Michael LohoffTak W Mak

Abstract

Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. Here, we show that CD4(+) T helper (Th) cells lacking IRF4 (IRF4(-/-)) are highly sensitive to apoptosis. After infection of IRF4(-/-) mice with the protozoan parasite Leishmania major, the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild-type mice after 4 wk, but demonstrated almost total loss of cellularity and enhanced apoptosis after 7 wk. In vitro, activation of IRF4(-/-) CD4(+) Th cells led to greatly increased apoptosis compared with wild-type cells. Coculture of IRF4(-/-) and IRF4(+/+) CD4(+) cells did not increase survival of IRF4(-/-) CD4(+) cells, indicating that the enhanced rate of IRF4(-/-) Th cell apoptosis was neither transferable nor due to lack of a cytokine. Enhanced CD4(+) cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4(-/-) and IRF4(+/+) cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4(-/-) CD4(+) cells despite normal expression of the IL-4 receptor. The...Continue Reading

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Citations

Jun 13, 2006·Nature Immunology·Ulf KleinRiccardo Dalla-Favera
Aug 7, 2007·Nature Immunology·Anne BrüstleMichael Lohoff
Feb 3, 2005·Nature Reviews. Immunology·Michael Lohoff, Tak W Mak
May 4, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nadine BolligMichael Lohoff
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Oct 17, 2020·Cytokine·Imtissal Krayem, Marie Lipoldová

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Lysys

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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