In situ analysis of B7-2 costimulatory, major histocompatibility complex class II, and adhesion molecule expression in schistosomal egg granulomas.
Immunopathological damage in schistosomiasis consist of egg granuloma formation, which is a hypersensitivity reaction mediated by antigen-specific CD4+ T helper (Th) lymphocytes. Th cells are dependent on accessory cell-bound co-stimulatory signals for activation. The B7 molecules provide critical costimulation, as in their absence T cells are rendered unresponsive. We investigated the kinetics of B7-2 molecule expression in schistosomal egg granulomas by immunocytochemical analysis in situ. We also monitored major histocompatibility complex (MHC) class II, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, as well as the presence of macrophages, T cells, and B cells. B7-2 expression was elevated in cells of the large granulomas of the acute (6-1/2 week) infection, and sharply declined thereafter. MHC class II expression was similarly elevated in the acute granulomas, but in contrast to B7-2, remained relatively constant throughout 12 1/2 weeks of infection. Moreover, ICAM-1 and VCAM-1 were expressed in acute and chronic granulomas. However, whereas ICAM-1 was constitutively expressed in normal liver, VCAM-1 was dramatically induced in the livers upon onset of disease. The findings suggest that the acute granulomas are rich in accessory cells with overall phenotypic configurations that support Th-cell activation, although at subsequent times, granulomas contain increasing numbers of B7-poor accessory cells capable of inducing Th-cell unresponsiveness. Thus, cellular interactions in early granulomas may be able to amplify egg-induced immunopathology, whereas interactions taking place in succeeding granulomas appear to precipitate its down-regulation.
Rathore
A
A
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Sacristán
C
C
Ricklan
D E
DE
Flores Villanueva
P O
PO
Stadecker
M J
MJ
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D001402:B-Lymphocytes / Q000473:pathology; D051940:B7-2 Antigen; D002452:Cell Count; D003713:Dendritic Cells / Q000737:chemistry; D005260:Female; D006099:Granuloma / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010063:Ovum / Q000469:parasitology / Q000473:pathology; D012552:Schistosomiasis / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1