Th2 cells shape the differentiation of developing T cell responses during interactions with dendritic cells in vivo.
During priming, naive CD4(+) Th cells differentiate into cells that produce either IFN-gamma or IL-4. Even though the cascade of pathways that induces IL-4-producing Th2 cells has been determined in vitro, the signals promoting Th2 differentiation under physiological conditions remain enigmatic, especially the natural role of the single most important Th2-inducing signal,IL-4. Using Th2 and naive Th cells, each expressing a distinct transgenic TCR, here we show that Th2 cells migrate with the same dynamics as naive Th cells in draining lymph nodes and bind to the same DC, when driven by antigen in complete Freund's adjuvant (CFA). Th2-cell-derived IL-4 deviates CFA-induced Th1 development toward a Th2 phenotype, if both cell populations co-localize in the same T cell area, and are activated simultaneously. Thus, intranodal Th2 cells directly influence Th cell differentiation in vivo, but only under restricted conditions. These findings have implications for the design of cytokine-based therapies and explain the spreading of Th2 responses to multiple aeroallergens in allergic asthma, where naive Th and Th2 cells co-localize in lung-draining lymph nodes.
Schipf
Alexander
A
Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany.
Heilmann
Annette
A
Boue
Laetitia
L
Mossmann
Horst
H
Brocker
Thomas
T
Röcken
Martin
M
D000595:Amino Acid Sequence; D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D005620:Freund's Adjuvant; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D005620:Freund's Adjuvant