Modification of specific antigen administered prior to transplantation and the route of administration shows promise for donor regulation of the immune response. Specifically, administration of Class I without Class II MHC antigen may prevent sensitization. In addition, pretransplant antigen administration via the portal vein prolongs allograft survival, presumably by processing of the antigen through the liver by an undefined mechanism. This proposal will examine parameters of the immune response to soluble and cellular alloantigens given via the portal vein compared to other routes of administration. Ovalbumin and its immunogenic peptide will be used to examine antigen processing and presentation to T-helper cells and the subsequent development of the delayed type hypersensitivity response, interleukins 1,2,3,4, and tumor necrosis factor (TNF) production. The response to native and heat or ultraviolet B irradiation (UVB) modified cellular alloantigen will be studied. Special attention will be given to the function and products of the Kupffer cells as compared with other macrophage populations. Specific adherence of antigen reactive cells (ARC) to Kupffer cells will be examined as a possible mechanism of sequestration and elimination of ARC. Since Kupffer cells produce prostaglandins and leukotrienes, the immunoregulatory effects of these products will be analyzed. The influence of these parameters on rejection will be examined by transplantation of parathyroid, kidney, heart, and liver allografts in rats. Immunological assessment of recipients of long surviving grafts will be examined for CTLp frequency, anti-idiotypic antibody, suppressor cells, and lymphokine production. In addition, a mouse sponge matrix allograft model will be employed to examine the kinetics of the responsible immune cell subpopulations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI028480-01A1
Application #
3143023
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Motoyama, K; Karl, I E; Flye, M W et al. (1999) Effect of Ca2+ agonists in the perfused liver: determination via laser scanning confocal microscopy. Am J Physiol 276:R575-85
Arima, T; Rehman, A; Flye, M W (1997) Reversal of CTLA4Ig-mediated tolerance to cardiac allografts by exogenous interleukin-2. Transplant Proc 29:1305-6
Hotchkiss, R S; Bowling, W M; Karl, I E et al. (1997) Calcium antagonists inhibit oxidative burst and nitrite formation in lipopolysaccharide-stimulated rat peritoneal macrophages. Shock 8:170-8
Tu, Y; Arima, T; Flye, M W (1997) Effect of donor irradiation or recipient interleukin-2 treatment on survival of spontaneously accepted rat liver allografts. Transplant Proc 29:856-7
Tu, Y; Arima, T; Flye, M W (1997) Effects of intrathymic tolerance on mouse heart and skin allograft acceptance. Transplant Proc 29:1063-4
Gillanders, W E; Arima, T; Tu, F et al. (1997) Evidence for clonal deletion and clonal anergy after intrathymic antigen injection in a transplantation model. Transplantation 64:1159-66
Tu, Y; Rehman, A; Flye, M W (1997) CTLA4-Ig treatment prolongs rat orthotopic liver graft survival. Transplant Proc 29:1036-7
Motoyama, K; Arima, T; Lehmann, M et al. (1997) Tolerance to heart and kidney grafts induced by nondepleting anti-CD4 monoclonal antibody (RIB 5/2) versus depleting anti-CD4 monoclonal antibody (OX-38) with donor antigen administration. Surgery 122:213-9; discussion 219-20
Tu, Y; Rehman, A; Flye, M W (1996) Prolongation of rat to mouse skin and heart xenograft survival by combined CTLA4Ig and anti-CD4/CD8 antibody. Transplant Proc 28:2061-2
Rehman, A; Tu, Y; Flye, M W (1996) Combined CTLA4Ig and anti-CD4/DC8 monoclonal antibody treatment prolongs survival of rat-to-mouse heterotopic cardiac xenografts. Transplant Proc 28:660-1

Showing the most recent 10 out of 43 publications