Abstract

Although the ultimate goal of this project is the development of specific modes of immunosuppression capable of promoting long term allograft survival with minimal side effects, elucidation of the structure and function of molecules involved in the cytolytic T lymphocyte (CTL) response represents an essential step towards this goal. For the past three years, we have studied lymphocyte function-associated antigens as defined by monoclonal antibodies which inhibit lymphocyte function. We propose here to expand these studies to antigens expressed by interleukin 2 (IL-2) dependent, antigen specific functional cytolytic T lymphocyte lines but which are not expressed by cells of other lineages or states of differentiation. Three complementary approached will be used to identify molecules limited to fully differentiated T cells: 1) subtractive absorption of polyspecific antisera; 2) subtractive immunization using tolerizing doses of anti-L3T4 antibody plus cellular antigen; and 3) substrative hybridization to identify T cell specific cDNA clones. The molecules so identified will be studied with regard to structure and function using the techniques of cellular immunology, protein chemistry, and molecular biology. The reagents and strategies so devised should prove useful as diagnostic and immunotherapeutic agents in organ transplantation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035008-07
Application #
3233240
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Ahn, Yong-Tae; Huang, Boli; McPherson, Lisa et al. (2007) Dynamic interplay of transcriptional machinery and chromatin regulates ""late"" expression of the chemokine RANTES in T lymphocytes. Mol Cell Biol 27:253-66
Song, An; Patel, Anita; Thamatrakoln, Kimberlee et al. (2002) Functional domains and DNA-binding sequences of RFLAT-1/KLF13, a Kruppel-like transcription factor of activated T lymphocytes. J Biol Chem 277:30055-65
Nikolcheva, Tania; Pyronnet, Stephane; Chou, Szu-yi et al. (2002) A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes. J Clin Invest 110:119-26
Schubert, Lisa A; Cron, Randy Q; Cleary, Aileen M et al. (2002) A T cell-specific enhancer of the human CD40 ligand gene. J Biol Chem 277:7386-95
Pardo, J; Perez-Galan, P; Gamen, S et al. (2001) A role of the mitochondrial apoptosis-inducing factor in granulysin-induced apoptosis. J Immunol 167:1222-9
Boytim, M L; Lilly, P; Drouvalakis, K et al. (2000) A human class II MHC-derived peptide antagonizes phosphatidylinositol 3-kinase to block IL-2 signaling. J Clin Invest 105:1447-53
Hanson, D A; Kaspar, A A; Poulain, F R et al. (1999) Biosynthesis of granulysin, a novel cytolytic molecule. Mol Immunol 36:413-22
Song, A; Chen, Y F; Thamatrakoln, K et al. (1999) RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. Immunity 10:93-103
Boytim, M L; Lyu, S C; Jung, R et al. (1998) Inhibition of cell cycle progression by a synthetic peptide corresponding to residues 65-79 of an HLA class II sequence: functional similarities but mechanistic differences with the immunosuppressive drug rapamycin. J Immunol 160:2215-22
Gamen, S; Hanson, D A; Kaspar, A et al. (1998) Granulysin-induced apoptosis. I. Involvement of at least two distinct pathways. J Immunol 161:1758-64

Showing the most recent 10 out of 32 publications