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Production Within the Granulomas of Murine Schistosomiasis in IL-4-Deficient and Control Mice1


Departments of
*
Internal Medicine and
Pathology, Divisions of Gastroenterology-Hepatology and Allergy, University of Iowa, Iowa City, IA 52242
Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice
make little IFN-
and show no Th1 polarization. This could signify
that these granulomas have few cells capable of IFN-
synthesis or
that such cells are under tight control. Granulomas can make IL-10 and
TGF-ß, which can regulate IFN-
synthesis. Using FACS analysis and
ELISA, we explored the origin and regulation of IFN-
in schistosome
granulomas from both IL-4-/- and
IL-4+/+ mice. FACS analysis of intracytoplasmic IFN-
staining showed that some granuloma Thy1.2+ T cells
(CD8+ and CD4+) express IFN-
. Granulomas had
NK1.1+ cells, but they appeared to produce little or no
IFN-
. Purified granuloma Thy1.2+ cells made IFN-
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-ß mAb or with rIL-12 substantially
increased T cell IFN-
synthesis, particularly in the
IL-4-/- animals. Cultured granuloma cells depleted of
Thy1.2+ lymphocytes by Ab and C released no IFN-
. It is
concluded that granuloma IFN-
comes from T cells, not NK cells.
Also, this T cell-derived IFN-
is subject to IL-10 and TGF-ß
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.
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