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*
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111; and
Immunology Research Division, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
The granulomatous inflammation in infection with the helminth
Schistosoma mansoni represents a cellular
hypersensitivity reaction mediated by, and dependent upon, MHC class
II-restricted CD4+ Th cells sensitized to parasite egg
Ags. The current work examines the role and significance of the
B7:CD28/CTLA-4 pathway in providing the costimulation necessary for the
activation of these pathogenic T cells. In vitro T cell responses in
B7-1-/- mice, 7–8 wk postinfection, were no different
from wild-type controls, but the absence of B7-2 molecules resulted in
a decrease in egg Ag-induced proliferation with increased IFN-
production. Both B7-1-/- and B7-2-/-
mice exhibited intact granuloma formation. In contrast,
CD4+ Th cells from B7-1/2 double-deficient mice displayed a
dramatic loss of proliferative capacity upon stimulation with egg Ag.
Most strikingly, these T cells secreted only IFN-, but not IL-4 and
IL-10, a pattern entirely opposite to that displayed by wild-type
controls. Despite these major differences in T cell reactivity,
B7-1/2-/- mice had only a limited reduction of granuloma
size and fibrosis, without appreciable difference in cellular
composition. These results show that substantial granuloma formation
can occur under conditions of limited T cell expansion and restricted
Th1-type cytokine production. They also support the notion that the
combined effect of B7 signaling is not as critical for Th1 cell
activation as it is for the development of the Th2 dominant environment
characteristic of the evolving schistosome infection in
H-2b mice.
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