While MHC-restricted T cell interactions with macrophages and B cells have been well-documented, little is known about T-T interactions between T cell subpopulations. During the past grant cycle we isolated and characterized several self-Ia reactive (autoreactive) Lyt 1+2-, L3T4+, Ia- T cell clones from normal unimmunized DBA/2 mice and used them to analyze the hypothesis that a T-T network existed in the normal immune system. These studies led to the unique observation that Lyt 1+2- T cells isolated from normal DBA/2 mice proliferated strongly and directly to syngeneic autoreactive T cells. Most recently preliminary data has indicated that normal Lyt 1+2 T cells respond to allogeneic as well as syngeneic autoreactive T cells suggesting that the T-T network may be """"""""monomorphic"""""""" with respect to class II antigens. Based on these observations studies will be carried out to: 1) Analyze selected characteristics of the T-t interaction between Lyt 1+2-, L3T4+, Ia- T cells and autoreactive T cells. 2) Test the hypothesis that the idiotypic markers of T cell receptors for MHC epitopes are """"""""monomorphic"""""""" within the species. 3) Analyze the rearrangement pattern, expression and sequence of T cell receptor genes for auto- and alloreactive T cell clones/hybridomas with specificity for Iad. 4) Analyze the function of autoreactive T cells and their regulation by Lyt 1+2-, L3T4- anti-autoreactive T cells. These studies will involve preparation of a series of autoreactive and anti- autoreactive T cell hybridomas and analysis of the hybridoma receptors by anti-autoreactive T cells and by anti-receptor monoclonal antibodies. The potential functional significance of Lyt 1+2-anti-autoreactive T cells will be analyzed in vitro to determine the modulatory effects of these cells on autoreactive T cells. Lastly, we will attempt to manipulate mice so as to be able to directly access the biologic effects of autoreactive T cells in vivo. These experiments should provide information relative to network regulation among T cells and its potential role in neoplasia, autoimmunity and regulation of graft versus host disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA034052-04A1
Application #
3171788
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-06-01
Project End
1992-03-31
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Bryson, J S; Lake-Bullock, H; Pflugh, D L et al. (1995) In vivo reactivity of T cell clones isolated from mice with syngeneic graft-versus-host disease. Transplantation 60:171-8
Barve, S S; Cohen, D A; De Benedetti, A et al. (1994) Mechanism of differential regulation of IL-2 in murine Th1 and Th2 T cell subsets. 1. Induction of IL-2 transcription in Th2 cells by up-regulation of transcription factors with the protein synthesis initiation factor 4E. J Immunol 152:1171-81
Cohen, D A; Fitzpatrick, E A; Barve, S S et al. (1993) Activation-dependent apoptosis in CD4+ T cells during murine AIDS. Cell Immunol 151:392-403
Bryson, J S; Jennings, C D; Caywood, B E et al. (1993) Thy1+ bone marrow cells regulate the induction of murine syngeneic graft-versus-host disease. Transplantation 56:941-5
Fitzpatrick, E A; Bryson, J S; Rhoads, C et al. (1992) T-deficient transmembrane signaling in CD4+ T cells of retroviral-induced immune-deficient mice. J Immunol 148:3377-84
Chang, J C; Zhang, L; Distler, S G et al. (1992) Characterization and function of CD3+ CD4- CD8- TcR-alpha beta bearing cells infiltrating the lung during the immune response. Reg Immunol 4:25-33
Bryson, J S; Jennings, C D; Caywood, B E et al. (1991) Strain specificity in the induction of syngeneic graft-versus-host disease in mice. Transplantation 51:911-3
Bryson, J S; Caywood, B E; Kaplan, A M (1991) Relationship of cyclosporine A-mediated inhibition of clonal deletion and development of syngeneic graft-versus-host disease. J Immunol 147:391-7
Bryson, J S; Jones, L A; Caywood, B E et al. (1990) In vivo regulation of the murine syngeneic mixed lymphocyte reaction. Cell Immunol 129:138-50
Bryson, J S; Jennings, C D; Caywood, B E et al. (1989) Induction of a syngeneic graft-versus-host disease-like syndrome in DBA/2 mice. Transplantation 48:1042-7

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