IL-18 stimulates the proliferation and IFN-gamma release of CD4+ T cells in the chicken: conservation of a Th1-like system in a nonmammalian species.
The phylogeny of Th1 and Th2 subsets has not been characterized mainly due to the limited information regarding cytokines in nonmammalian vertebrates. In this study, we characterize a Th1-like regulatory system focusing on the IL-18-regulated IFN-gamma secretion. Stimulation of splenocytes with chicken IL-18 induced high levels of IFN-gamma secretion. Depletion of either macrophages or CD4(+) T cells from the splenocyte cultures caused unresponsiveness to IL-18. In contrast, PBL were unresponsive to IL-18 in the presence or absence of macrophages, but IFN-gamma secretion was stimulated by suboptimal anti-TCR cross-linking combined with IL-18. Splenocytes from five different chicken lines responded equally well to the IL-18 treatment. LSL chicken splenocytes, however, responded only to IL-18 when stimulated either with optimal TCR cross-linking alone or suboptimal TCR cross-linking combined with IL-18. IL-18 not only induced IFN-gamma secretion, but also stimulated splenocyte proliferation. This IL-18-induced proliferation was compared with the effects observed with IL-2. Both cytokines activated the splenocytes as demonstrated by increased size and MHC class II Ag up-regulation in the case of IL-18. Phenotypic analyses following 6 days of culture revealed that IL-2 mainly affected the proliferation of CD8(+) cells, whereas IL-18 had an opposite effect and stimulated the proliferation of CD4(+) cells. Taken together, these results demonstrate the conservation of Th1-like proinflammatory responses in the chicken; they characterize IL-18 as a major growth factor of CD4(+) T cells and identify two distinct mechanisms of IL-18-induced IFN-gamma secretion.
Göbel
Thomas W
TW
Institute for Animal Physiology, University of Munich, Munich, Germany.
Schneider
Kirsten
K
Schaerer
Beatrice
B
Mejri
Iris
I
Puehler
Florian
F
Weigend
Steffen
S
Staeheli
Peter
P
Kaspers
Bernd
B
D000818:Animals; D017849:Animals, Inbred Strains; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D002645:Chickens / Q000276:immunology*; D003432:Cross-Linking Reagents / Q000378:metabolism; D007108:Immune Tolerance; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D020382:Interleukin-18 / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D010802:Phylogeny; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D020382:Interleukin-18; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma