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.
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).
Tumor Immunology Program German Cancer Research Center, and Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany. Benedikt.Fritzching@dkfz.de
Benedikt
B
Fritzsching
Nina
N
Oberle
Nadine
N
Eberhardt
Sabine
S
Quick
Jürgen
J
Haas
Brigitte
B
Wildemann
Peter H
PH
Krammer
Elisabeth
E
Suri-Payer
D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C505661:FASLG protein, human; C418974:FOXP3 protein, human; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2