A major theme of this program project is the study of accessory cell function required for the stimulation of T helper cells. The two functions that are investigated are the expression and role of two key molecules: interleukin-1 and the class II histocompatibility molecules, or Ia molecules. Two of the projects deal with basic issues concerning some of the regulatory mechanisms that lead to IL-1 and Ia production by antigen presenting cells. Attempts are described to modulate Ia expression mainly by the use of by antibodies to interferon- gamma. The effects of this manipulation in the transplantation of allogeneic tissues is critically analyzed with a number of tissues. One of our objectives is to integrate the activity of basic immunobiologists with transplantation surgeons by creating a program where both activities are deeply interrelated for the benefit of both groups.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI024854-02
Application #
3091827
Study Section
Allergy, Immunology, and Transplantation Research Committee (AITC)
Project Start
1987-09-01
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
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
Nett-Fiordalisi, M; Tomaselli, K; Russell, J H et al. (1995) Macrophage apoptosis in the absence of active interleukin-1 beta-converting enzyme. J Leukoc Biol 58:717-24
Mariathasan, S; Matsumoto, M; Baranyay, F et al. (1995) Absence of lymph nodes in lymphotoxin-alpha(LT alpha)-deficient mice is due to abnormal organ development, not defective lymphocyte migration. J Inflamm 45:72-8
Sheehan, K C; Pinckard, J K; Arthur, C D et al. (1995) Monoclonal antibodies specific for murine p55 and p75 tumor necrosis factor receptors: identification of a novel in vivo role for p75. J Exp Med 181:607-17
Wall, D A; Sheehan, K C (1994) The role of tumor necrosis factor and interferon gamma in graft-versus-host disease and related immunodeficiency. Transplantation 57:273-9
Goss, J A; Nakafusa, Y; Flye, M W (1993) MHC class II presenting cells are necessary for the induction of intrathymic tolerance. Ann Surg 217:492-9;discussion 499-501
Gerasimidi, A; Sheehan, K C; Schreiber, R D et al. (1993) Tumor necrosis factor-alpha prevents rejection of islet xenografts (rat to mouse). Diabetes 42:651-7
Dighe, A S; Farrar, M A; Schreiber, R D (1993) Inhibition of cellular responsiveness to interferon-gamma (IFN gamma) induced by overexpression of inactive forms of the IFN gamma receptor. J Biol Chem 268:10645-53
Schreiner, G F; Kamei, T; Lefkowith, J et al. (1993) Modulation of the kinetics of the initial leukocyte migration into renal allografts by 16,16-dimethyl PGE2. Transplantation 56:417-22
Nakafusa, Y; Goss, J A; Mohanakumar, T et al. (1993) Induction of donor-specific tolerance to cardiac but not skin or renal allografts by intrathymic injection of splenocyte alloantigen. Transplantation 55:877-82
Carel, J C; Sheehan, K C; Schreiber, R D et al. (1993) Prevention of rejection of transforming growth factor beta-treated rat-to-mouse islet xenografts by monoclonal antibody to tumor necrosis factor. Transplantation 55:456-8

Showing the most recent 10 out of 45 publications