The overall objective of this proposal is to define the cause and possibly the etiology of the intrinsic defect(s) in the function of T-cells and their subsets obtained from patients with malignant primary intracranial tumors. Experiments are designed to investigate this defect(s) by activating T-cells from patients by employing a monoclonal antibody which interacts with the T3-Ti receptor complex. Activated T-cells and their subsets obtained from patients will be examined for their proliferative capacity. Early activation events occurring after stimulation of T-cells with OKT3 monoclonal antibody will also be examined. These will include measurement of Ca2+ mobilization, the generation of a phosphatidylinositol cycle, protein kinase C activity as well as the expression of protooncogenes. The mobilization of Ca2+ will be quantitated employing the Ca2+ chelator quin 2 while the phosphatidylinositol cycle will be measured by the incorporation of 3/H-inositol into phospholipids. The protooncogenes will be quantitated by employing appropriate cDNA probes using dot and Northern blot analysis. The final series of experiments will define the role of immunoregulatory moeities secreted by human glial tumors in modulating the activation and proliferation of T-cells obtained from normal individuals. Culture supernatants obtained from glial tumor cell lines will be fractionated to isolate and characterize the inhibitory factor(s). This inhibitory factor(s) will be employed to determine whether when added to normal T-cells it can reproduce the defect(s) observed with T-cells obtained from patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA018234-10A1
Application #
3164885
Study Section
Experimental Immunology Study Section (EI)
Project Start
1976-06-01
Project End
1992-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
10
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