Previously we determined the dynamics of spontaneous regression of egg antigen (SEA) induced mitogenesis of spleen cells (SC), of delayed hypersensitivity to SEA and of hepatic granulomatous inflammation during infection of C57Bl/6 mice with Schistosoma japonica. IgGl from the serum of chronically infected mice caused regression of the blastogenesis in vitro and of hepatic granulomas (HG) upon passive transfer into acutely infected mice. During the first 2 years of this grant we showed: supression of SC mitogenesis by Lyt 2+ splenic T cells from mice infected for 10 weeks or longer; suppression of HG by T cells from mice infected for 10 weeks or longer; synergy between IgGl (or serum) and T-cell mediated suppression of in vitro SC mitogenesis and in vivo HG formation; production by B cell hybridomas of factors (largely non Sea-binding) which suppress SC mitogenesis; reduced production of IL-2 and interferon (IFN) during infection; depressed cellular and humoral immunity to injected myoglobin during infection. A revised working hypothesis and the following questions form the basis of this grant: 1. What are the kinetics, specificity, mechanisms and phenotypes of cells in regulation? 2. What is the role of antibody to SEA, including monoclonal antibodies in humoral regulation? 3. What are the mechanisms, kinetics, and specificity of humoral regulation? 4. What are the cells, kinetics, molecules, and mechanisms--especially the role of Fc of immunoglobulin and of immune complexes--involved in the synergy between humoral and cellular regulatory mechanisms? 5. Is the HG a correlate of cell-mediated immunity? 6. What is the role of the HG per se in the disease: what molecule does it produce which contribute to its pathogenesis; what molecules does it produce which contribute to its own regulation; are its architecture and cell composition altered during infection? 7. Is the failure of lymphokine production (IL-2, IFN) during infection due to central failure, failure of utilization or to supression of production? In addition to the use of SEA-induced SC blastogenesis, the production of IL-2, IFN and macrophage activity factors in response to Concanavalin A and SEA will be employed as in vitro targets for regulation. Both pulmonary and hepatic granulomatous inflammation will be employed as targets for regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
2R22AI018523-04
Application #
3444567
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1982-07-01
Project End
1988-08-31
Budget Start
1985-09-30
Budget End
1986-08-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Stavitsky, Abram B (2004) Regulation of granulomatous inflammation in experimental models of schistosomiasis. Infect Immun 72:1-12
Olds, G R; Kresina, T F (1990) Characterization of a family of monoclonal antibodies which bind Schistosoma japonicum egg antigens and express an interstrain cross-reactive idiotype. Parasite Immunol 12:199-211
Stavitsky, A B; Harold, W W (1989) Deficiency of interleukin-2 production upon addition of soluble egg antigen to cultures of isolated hepatic granulomas or hepatic granuloma cells from mice infected with Schistosoma japonicum. Infect Immun 57:2339-44
Stavitsky, A B; Harold, W W (1988) Deficiency of interleukin-2 activity upon addition of soluble egg antigen to cultures of spleen cells from mice infected with Schistosoma japonicum. Infect Immun 56:1778-84
Olds, G R; Stavitsky, A B (1986) Mechanisms of in vivo modulation of granulomatous inflammation in murine schistosomiasis japonicum. Infect Immun 52:513-8
Olds, G R; Finegan, C; Kresina, T F (1986) Dynamics of hepatic glycosaminoglycan accumulation in murine Schistosoma japonicum infection. Gastroenterology 91:1335-42
Olds, G R; Kresina, T F (1985) Network interactions in Schistosoma japonicum infection. Identification and characterization of a serologically distinct immunoregulatory auto-antiidiotypic antibody population. J Clin Invest 76:2338-47
Olds, G R; Griffin, A; Kresina, T F (1985) Dynamics of collagen accumulation and polymorphism in murine Schistosoma japonicum. Gastroenterology 89:617-24
Stavitsky, A B; Olds, G R; Peterson, L B (1985) Regulation of egg antigen-induced in vitro proliferative response by splenic suppressor T cells in murine Schistosoma japonicum infection. Infect Immun 49:635-40