In situ analysis of B7-2 costimulatory, major histocompatibility complex class II, and adhesion molecule expression in schistosomal egg granulomas

• Published in: The American journal of pathology Vol. 149; no. 1; pp. 187 - 194
• Main Authors: Rathore, A, Sacristan, C, Ricklan, DE, Flores Villanueva, PO, Stadecker, MJ
• Format: Journal Article
• Language: English
• Published: United States ASIP 01.07.1996; American Society for Investigative Pathology
• Subjects: Animals; Antigens, CD - analysis; B-Lymphocytes - pathology; B7-2 Antigen; Cell Count; Dendritic Cells - chemistry; Female; Granuloma - pathology; Histocompatibility Antigens Class II - analysis; Immunohistochemistry - methods; Intercellular Adhesion Molecule-1 - analysis; Liver - chemistry; Liver - pathology; Membrane Glycoproteins - analysis; Mice; Mice, Inbred C57BL; Ovum - parasitology; Ovum - pathology; Schistosomiasis - pathology; T-Lymphocytes - pathology; Vascular Cell Adhesion Molecule-1 - analysis
• ISSN: 0002-9440; 1525-2191

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.