In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly susceptible to CD95 ligand- but not to TCR-mediated cell death

Benedikt Fritzsching; Nina Oberle; Nadine Eberhardt; Sabine Quick; Jürgen Haas; Brigitte Wildemann; Peter H Krammer; Elisabeth Suri-Payer

doi:10.4049/jimmunol.175.1.32

In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly susceptible to CD95 ligand- but not to TCR-mediated cell death

J Immunol. 2005 Jul 1;175(1):32-6. doi: 10.4049/jimmunol.175.1.32.

Authors

Benedikt Fritzsching¹, Nina Oberle, Nadine Eberhardt, Sabine Quick, Jürgen Haas, Brigitte Wildemann, Peter H Krammer, Elisabeth Suri-Payer

Affiliation

¹ Tumor Immunology Program German Cancer Research Center, and Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany. Benedikt.Fritzching@dkfz.de

PMID: 15972628
DOI: 10.4049/jimmunol.175.1.32

Abstract

CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) suppress T cell function and protect rodents from autoimmune disease. Regulation of T(reg) during an immune response is of major importance. Enhanced survival of T(reg) is beneficial in autoimmune disease, whereas increased depletion by apoptosis is advantageous in cancer. We show here that freshly isolated FACS-sorted T(reg) are highly sensitive toward CD95-mediated apoptosis, whereas other T cell populations are resistant to CD95-induced apoptosis shortly after isolation. In contrast, TCR restimulation of T(reg) in vitro revealed a reduced sensitivity toward activation-induced cell death compared with CD4(+)CD25(-) T cells. Thus, the apoptosis phenotype of T(reg) is unique in comparison to other T cells, and this might be further explored for novel therapeutic modulations of T(reg).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / immunology
Base Sequence
CD4-Positive T-Lymphocytes / cytology*
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism
DNA, Complementary / genetics
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Fas Ligand Protein
Forkhead Transcription Factors
Humans
In Vitro Techniques
Lymphocyte Activation
Membrane Glycoproteins / metabolism
Receptors, Antigen, T-Cell / metabolism
Receptors, Interleukin-2 / metabolism
T-Lymphocyte Subsets / cytology*
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism

Substances

DNA, Complementary
DNA-Binding Proteins
FASLG protein, human
FOXP3 protein, human
Fas Ligand Protein
Forkhead Transcription Factors
Membrane Glycoproteins
Receptors, Antigen, T-Cell
Receptors, Interleukin-2