Effects of interleukin 4 on CD25+CD4+ regulatory T cell function.
CD25+CD4+ regulatory T cells (Tregs) contribute to the maintenance of peripheral tolerance against self and non-self. The modulatory effects of cytokines, such as interleukin 4 (IL-4) on the function of Tregs have not been explored in detail. We here report that IL-4 prevents spontaneous apoptosis and the decline of foxp3 mRNA which were found to occur during culture of isolated Tregs. Tregs exposed to IL-4 were more potent in suppressing the proliferation of naïve CD4+ T cells and they better inhibited IFN-gamma production by CD4+ T cells as compared to Tregs cultured in medium. IL-4 also enhanced membrane IL-2Ralpha (CD25) expression on Tregs above the levels observed on freshly isolated cells. IL-4-mediated effects on Treg function persisted in Tregs from Stat6-/- mice, pointing to a Stat6-independent intracellular transduction pathway. In conclusion, our data suggest that the anti-inflammatory function of IL-4 could partly be mediated by effects on Tregs function.
Maerten
Philippe
P
Laboratory of Experimental Immunology, University Hospital, Katholieke Universiteit Leuven, Belgium.
Shen
Chong
C
Bullens
Dominique M A
DM
Van Assche
Gert
G
Van Gool
Stefaan
S
Geboes
Karel
K
Rutgeerts
Paul
P
Ceuppens
Jan L
JL
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D006131:Growth Inhibitors / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006131:Growth Inhibitors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma