Cutting edge: IL-4-induced protection of CD4+CD25- Th cells from CD4+CD25+ regulatory T cell-mediated suppression.
CD4(+)CD25(+) T regulatory (Treg) cells are a CD4(+) T cell subset involved in the control of the immune response. In vitro, murine CD4(+)CD25(+) Treg cells inhibit CD4(+)CD25(-) Th cell proliferation induced by anti-CD3 mAb in the presence of APCs. The addition of IL-4 to cocultured cells inhibits CD4(+)CD25(+) Treg cell-mediated suppression. Since all cell types used in the coculture express the IL-4Ralpha chain, we used different combinations of CD4(+)CD25(-) Th cells, CD4(+)CD25(+) Treg cells, and APCs from wild-type IL-4Ralpha(+/+) or knockout IL-4Ralpha(-/-) mice. Results show that the engagement of the IL-4Ralpha chain on CD4(+)CD25(-) Th cells renders these cells resistant to suppression. Moreover, the addition of IL-4 promotes proliferation of IL-4Ralpha(+/+)CD4(+)CD25(+) Treg cells, which preserve full suppressive competence. These findings support an essential role of IL-4 signaling for CD4(+)CD25(-) Th cell activation and indicate that IL-4-induced proliferation of CD4(+)CD25(+) Treg cells is compatible with their suppressive activity.
Department of Biology, University of Rome Tor Vergata, Italy.
Luigia
L
Pace
Stefania
S
Rizzo
Cecilia
C
Palombi
Frank
F
Brombacher
Gino
G
Doria
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D015847:Interleukin-4