The focus of this proposal is a molecular evaluation of the helper T cell response in anti-tubular basement membrane disease (alphaTBM disease). Murine alphaTBM disease is an model of autoimmune interstitial nephritis, which has significant relevance to many forms of human renal disease. The helper T cell is a central and essential mediator of the nephritogenic immune response in this model. I plan to investigate the molecular immunoregulatory consequences of the interaction between cultured nephritogenic helper T cells and their target/antigen presenting cells, a renal proximal tubular cell line. I will also more precisely characterize the molecular structure of the T cell receptor repertoire Inducing the nephritogenic immune response. Finally, I plan to analyze and characterize the cDNA for the antigen binding chain of T helper factor (ThF), a unique antigen-specific, MHC II-restricted soluble cytokine that mediates alphaTBM disease. The underlying focus of all of these related projects is to better understand the basic molecular mechanisms of autoimmunity and to identify potential sites for specific therapeutic intervention. The work will collectively utilize a variety of molecular biological and cell culture techniques, that I have mastered over the past two years, to accomplish these goals.
| Matesic, D; Lehmann, P V; Heeger, P S (1998) High-resolution characterization of cytokine-producing alloreactivity in naive and allograft-primed mice. Transplantation 65:906-14 |
| Valujskikh, A; Matesic, D; Gilliam, A et al. (1998) T cells reactive to a single immunodominant self-restricted allopeptide induce skin graft rejection in mice. J Clin Invest 101:1398-407 |
| Tary-Lehmann, M; Hricik, D E; Justice, A C et al. (1998) Enzyme-linked immunosorbent assay spot detection of interferon-gamma and interleukin 5-producing cells as a predictive marker for renal allograft failure. Transplantation 66:219-24 |
| Heeger, P S; Neilson, E G (1994) Overcoming tolerance in autoimmune renal disease. Curr Opin Nephrol Hypertens 3:123-32 |
