Cutting edge: IL-12 induces CD4+CD25- T cell activation in the presence of T regulatory cells.
IL-12p40 cytokines have been implicated in the development of organ-specific autoimmune diseases as well as pathogen-specific adaptive immunity. In addition to inducing IFN-gamma, IL-12 stimulates effector CD4(+) T cells to express adhesion molecules and homing receptors that facilitate their migration to sites of inflammation. In this study, we expand upon those observations by demonstrating an alternative pathway by which IL-12 could promote Th1 inflammatory responses in mice, namely, by restoring proliferation and cytokine expression by effector T cells in the presence of CD4(+)CD25(+) regulatory T cells (Treg). This effect of IL-12 was not replicated by IL-23 or IFN-gamma and was dependent on signaling through the IL-12R expressed on CD25(-) responder cells, but not on Treg. Our studies suggest that IL-12 could act in concert with other proinflammatory factors to stimulate CD4(+)CD25(-) T cell activation in the presence of Treg.
Interdepartmental Graduate Program in Neuroscience, Department of Neurology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Irah L
IL
King
Benjamin M
BM
Segal
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D053707:Receptors, Interleukin-12; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C508841:Il23a protein, mouse; D007376:Interleukin-2; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D021122:Protein Subunits; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma