Recent advances in immunologic techniques permit the cloning and maintenance of human T-cells that are then available for detailed scientific study. In addition, monoclonal antibodies have been developed that recognize human T-lymphocytes at various stages of differentiation and identify different functional categories of T-cells. Anti-Ta1 is one such monoclonal antibody that reacts with activated T-cells that are more prevalent in the blood of multiple sclerosis patients compared to controls. These approaches will be used for a series of detailed investigations of cellular immunologic studies of central nervous system inflammatory disease, with particular emphasis on multiple sclerosis, a presumed autoimmune disease of the central nervous system associated with abnormalities of cellular immunity. The specific areas of investigation and questions to be asked are as follows: 1. What are the phenotypes and functional characteristics of activation antigen positive cells in the blood and spinal fluid of MS patients and patients with other inflammatory CNS diseases? 2. Using direct single cell clonal analysis of blood and cerebrospinal fluid T-lymphocytes, what is the frequency of different T-cell subpopulations using functional and phenotypic analysis? 3. Are there deficiencies in white matter antigen specific T8 suppressor cells which are induced by T4 suppressor/inducer cells in patients with multiple sclerosis? 4. What are the effects of virus on in vitro immune function and, in particular, the interaction of reovirus type 3 with specific T-cell subpopulations that have a receptor for the viral hemagglutinin?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS000981-03
Application #
3083588
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1985-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Hafler, D A; Cohen, I; Benjamin, D S et al. (1992) T cell vaccination in multiple sclerosis: a preliminary report. Clin Immunol Immunopathol 62:307-13
Brod, S A; Benjamin, D; Hafler, D A (1991) Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease. J Immunol 147:810-5
Lee, S J; Wucherpfennig, K W; Brod, S A et al. (1991) Common T-cell receptor V beta usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis. Ann Neurol 29:33-40
LaSalle, J M; Hafler, D A (1991) The coexpression of CD45RA and CD45RO isoforms on T cells during the S/G2/M stages of cell cycle. Cell Immunol 138:197-206
Hafler, D A; Chofflon, M; Kurt-Jones, E et al. (1991) Interleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis. Clin Immunol Immunopathol 58:115-25
Brod, S A; Purvee, M; Benjamin, D et al. (1990) T-T cell interactions are mediated by adhesion molecules. Eur J Immunol 20:2259-68
Brod, S A; Purvee, M; Benjamin, D et al. (1990) Frequency analysis of CD4+CD8+ T cells cloned with IL-4. Cell Immunol 125:426-36
Wucherpfennig, K W; Ota, K; Endo, N et al. (1990) Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science 248:1016-9
Hafler, D A; Chofflon, M; Benjamin, D et al. (1989) Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression. J Immunol 142:2590-6
Brod, S A; Rudd, C E; Purvee, M et al. (1989) Lymphokine regulation of CD45R expression on human T cell clones. J Exp Med 170:2147-52

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