Differential regulatory capacity of CD25+ T regulatory cells and preactivated CD25+ T regulatory cells on development, functional activation, and proliferation of Th2 cells.
CD25+ T regulatory (Treg) cells play a central role regarding the maintenance of peripheral tolerance via suppression of autoaggressive CD4+ T cells, CD8+ T cells, and Th1 cells. In this study we demonstrate that CD25+ Treg cells can also suppress the differentiation of murine conventional CD4+ T cells toward Th2 cells in a contact-dependent manner. However, the cytokine production and proliferation of established Th2 cells could not be inhibited by freshly isolated CD25+ Treg cells, whereas a strong inhibition of differentiated Th2 cells by in vitro preactivated CD25+ Treg cells could be observed. Inhibition of both conventional CD4+ T cells and Th2 cells is accompanied by a strong enhancement of the expression of FoxP3 in the suppressed T cells. Hence, our study indicates that CD25+ Treg cells have a therapeutic potential for Th2-mediated diseases and suggests a novel mechanism of suppression mediated by the transcriptional repressor FoxP3.
Stassen
Michael
M
Institute of Immunology, Johannes Gutenberg University, Hochhaus am Augustusplatz, D-55101 Mainz, Germany.
Jonuleit
Helmut
H
Müller
Christian
C
Klein
Matthias
M
Richter
Christoph
C
Bopp
Tobias
T
Schmitt
Steffen
S
Schmitt
Edgar
E
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D005452:Fluoresceins / Q000378:metabolism; D051858:Forkhead Transcription Factors; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013388:Succinimides / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D016207:Cytokines; D004268:DNA-Binding Proteins; D005452:Fluoresceins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2; D013388:Succinimides