Abstract

Murine SLE is an appropriate model for human SLE, since most, if not all of the immunological abnormalities fundamental to human SLE can also be readily observe in the murine system. The MHL1pr/1pr mouse is one of the strains that spontaneously develop SLE. In addition, all 1pr/1pr mice develop massive generalized lymph node enlargements as the disease progresses. In these enlarged lymph nodes, more than 90% of the cells are T cells. This project is concerned mainly with the in vitro physiology and immunobiology of the abnormal T cells in 1pr/1pr mice, and the relationship between in vitro T cell abnormalities and development of autoimmunity in vivo. Our research goals are summarized as follows: 1). Characterization of responsiveness of each individual T cell subpopulation in 1pr/1pr mice to receptor driven activation signals or polyclonal activators. 2). Characterization of the consequence of activation in vitro with respect to cell surface phenotypes and their differentiation state. Correlation between in vitro observations and in vivo pathogenesis. 3) Characterization of immune abnormalities in vitro and the establishment of an in vitro model system for the study of differentiation of 1pr/1pr T cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR038018-02
Application #
3158377
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1987-05-01
Project End
1988-09-30
Budget Start
1988-05-01
Budget End
1988-09-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Ah-Kim, H; Zhang, X; Islam, S et al. (2000) Tumour necrosis factor alpha enhances the expression of hydroxyl lyase, cytoplasmic antiproteinase-2 and a dual specificity kinase TTK in human chondrocyte-like cells. Cytokine 12:142-50
Haqqi, T M; Qu, X M; Anthony, D et al. (1996) Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice. J Clin Invest 97:2849-58
Guo, Y J; Lin, S C; Wang, J H et al. (1994) Palmitoylation of CD44 interferes with CD3-mediated signaling in human T lymphocytes. Int Immunol 6:213-21
Guo, Y; Ma, J; Wang, J et al. (1994) Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 54:1561-5
Guo, Y J; Ma, J; Wong, J H et al. (1993) Monoclonal anti-CD44 antibody acts in synergy with anti-CD2 but inhibits anti-CD3 or T cell receptor-mediated signaling in murine T cell hybridomas. Cell Immunol 152:186-99
Ley, S C; Tan, K N; Kubo, R et al. (1989) Surface expression of CD3 in the absence of T cell receptor (TcR): evidence for sorting of partial TcR/CD3 complexes in a post-endoplasmic reticulum compartment. Eur J Immunol 19:2309-17
Stafford-Brady, F; Sugiyama, E; Robinson, D R et al. (1989) Defective signal transduction in CD4-CD8- T cells of lpr mice. Cell Immunol 123:396-404
Yamada, K; Spezialetti, R; Marshak-Rothstein, A et al. (1989) Autoantibody in MRL/Mp-lpr/lpr mice. A monoclonal antibody specific for the abnormal T cells from mice bearing the lpr/lpr gene. J Immunol 142:2702-7
Sleckman, B P; Bigby, M; Greenstein, J L et al. (1989) Requirements for modulation of the CD4 molecule in response to phorbol myristate acetate. Role of the cytoplasmic domain. J Immunol 142:1457-62
Weston, K M; Ju, S T; Lu, C Y et al. (1988) Autoreactive T cells in MRL/Mpr-lpr/lpr mice. Characterization of the lymphokines produced and analysis of antigen-presenting cells required. J Immunol 141:1941-8