Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice.
Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN-gamma and show no Th1 polarization. This could signify that these granulomas have few cells capable of IFN-gamma synthesis or that such cells are under tight control. Granulomas can make IL-10 and TGF-beta, which can regulate IFN-gamma synthesis. Using FACS analysis and ELISA, we explored the origin and regulation of IFN-gamma in schistosome granulomas from both IL-4(-/-) and IL-4(+/+) mice. FACS analysis of intracytoplasmic IFN-gamma staining showed that some granuloma Thy1.2+ T cells (CD8+ and CD4+) express IFN-gamma. Granulomas had NK1.1+ cells, but they appeared to produce little or no IFN-gamma. Purified granuloma Thy1.2+ cells made IFN-gamma in vitro, whereas isolated NK1.1+ lymphocytes secreted little even with rIL-12 stimulation. Culture of granuloma cells with blocking anti-IL-10 or anti-TGF-beta mAb or with rIL-12 substantially increased T cell IFN-gamma synthesis, particularly in the IL-4(-/-) animals. Cultured granuloma cells depleted of Thy1.2+ lymphocytes by Ab and C released no IFN-gamma. It is concluded that granuloma IFN-gamma comes from T cells, not NK cells. Also, this T cell-derived IFN-gamma is subject to IL-10 and TGF-beta regulation, which is particularly evident in IL-4(-/-) mice. Thus, the Th2 granuloma of schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are under tight restraint.
Rakasz
E
E
Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
Blum
A M
AM
Metwali
A
A
Elliott
D E
DE
Li
J
J
Ballas
Z K
ZK
Qadir
K
K
Lynch
R
R
Weinstock
J V
JV
D000818:Animals; D005260:Female; D006099:Granuloma / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000172:deficiency / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012552:Schistosomiasis / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma