Co-activation of naive CD4+ T cells and bone marrow-derived mast cells results in the development of Th2 cells.
Activation of naive dense CD4+ T cells by plate-bound anti-CD3 antibodies favors the development of Th1 cells which, upon re-stimulation, produce significant amounts of IFN-gamma but no IL-4. However, co-activation of such naive T cells in the presence of IgE [anti-dinitrophenyl (DNP)]-loaded bone marrow-derived mast cells (BMMC) on plates coated with anti-CD3 antibodies and DNP-BSA led to the development of IL-4-producing Th2 cells. The same result could be observed if irradiated (800 rad) BMMC were applied as co-stimulators. Moreover, BMMC could be replaced by the supernatant of IgE-activated BMMC suggesting that a soluble mediator, presumably IL-4, was responsible for this effect. This assumption was substantiated using neutralizing anti-IL-4 antibodies which abolished the BMMC-mediated Th2 development in all cases. Addition of IL-12, a cytokine that was shown to antagonize the Th2-promoting effect of IL-4 in vivo, could not inhibit the development of IL-4-producing T cells, but gave rise to a T cell population which produced relatively high amounts of IL-4 and IFN-gamma. Since BMMC represent the in vitro equivalent of mucosal mast cells these data suggest that IgE-activated mucosal mast cells can bias an emerging T cell dependent immune response towards a Th2 dominated reaction by the initial production of IL-4.
Huels
C
C
Institut für Immunologie, University of Mainz, Germany.
Germann
T
T
Goedert
S
S
Hoehn
P
P
Koelsch
S
S
Hültner
L
L
Palm
N
N
Rüde
E
E
Schmitt
E
E
D000818:Animals; D001854:Bone Marrow Cells; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017455:Receptors, IgE / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology*
D017252:CD3 Complex; D016207:Cytokines; D017455:Receptors, IgE; D015847:Interleukin-4; D015759:Ionomycin