Abstract

The goal of this application is to investigate the regulation of autoreactive T lymphocytes. We have found that splenic T cells are stimulated to divide by T:T hybridomas specific for the MHC class II antigens of the T cell donor. These T cells appear to respond to idiotypic determinants on the T cell receptor on the T:T hybridomas.
The specific aims of this grant are to: 1. establish the molecules on the stimulatory cells that are recognized; 2. demonstrate that T cells which are specific for self MHC class II antigens (Type I autoreactive T cells) also stimulate autologous splenic T cells (Type II autoreactive T cells); 3. investigate the relationship between autoreactive T cells and antigen-specific T cells with high affinity for self MHC class II antigens; and 4. assess the immunoregulatory functions of Type I and Type II autoreactive T cells with respect to self tolerance and the immune response to foreign antigens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA026344-09
Application #
3167255
Study Section
Immunobiology Study Section (IMB)
Project Start
1979-07-01
Project End
1989-12-31
Budget Start
1987-07-01
Budget End
1988-12-31
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Weksler, M E; Schwab, R; Huetz, F et al. (1990) Cellular basis for the age-associated increase in autoimmune reactions. Int Immunol 2:329-35
Weksler, M E; Tsuda, T; Kim, Y T et al. (1990) Immunobiology of aging and cancer. Cancer Detect Prev 14:609-11
Weksler, M E; Schwab, R; Huetz, F et al. (1989) Cellular basis of autoantibody production in old mice. Trans Assoc Am Physicians 102:55-8
Innes, J B; Garbrecht, F C; Weksler, M E et al. (1989) Lymphocyte transformation induced by autologous cells. XVI: Distinctive role of discrete regions of class I MHC antigens in the autologous mixed leucocyte reaction. Clin Exp Immunol 75:280-5
Kennedy, D W; Weksler, M E; Russo, C (1988) Peripheral but not thymic T cells participate in an autoreactive T cell network. Cell Immunol 117:177-87
Tsuda, T; Kim, Y T; Siskind, G W et al. (1987) Role of the thymus and T-cells in slow growth of B16 melanoma in old mice. Cancer Res 47:3097-100
Kim, Y T; Puntillo, E; DeBlasio, T et al. (1987) Regulation of antibody production by hybridoma cultures. I. Anti-idiotype antibody-mediated down-regulation of anti-DNA antibody production by hybridoma cells. Cell Immunol 105:65-74
Garbrecht, F C; Siskind, G W; Weksler, M E (1987) Lymphocyte transformation induced by autologous cells: XVIII. Impaired autologous mixed lymphocyte reaction in subjects with AIDS-related complex. Clin Exp Immunol 67:245-51
Schwab, R; Crow, M K; Russo, C et al. (1985) Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol 135:1714-8
Bovbjerg, D H; Wang, V A; Schwab, R et al. (1985) Lymphocyte transformation induced by autologous cells. XVII. Lower autologous mixed lymphocyte reaction in subjects with a history of hayfever. Int Arch Allergy Appl Immunol 78:332-4