The research described in this proposal will investigate T lymphocyte function abnormalities in autoimmune thrombocytopenia (ATP) and study genetic mechanisms which lead to this dysfunction. Purified T and B lymphocytes will be obtained from control subjects and ATP patients. B cells will be infected with Epstein-Barr Virus (EBV) and regulation of EBV induced immunoglobulin (Ig) secretion by control or ATP T cells will be compared. Measurement of both total and antiplatelet specific Ig will allow further characterization of the immune regulatory disorder in ATP. In separate experiments, control or ATP lymphocytes will be treated with ATP plasma and complement to identify cytotoxic anti T cell antibodies. Sera with anti T cell activity will be assayed for the ability to modulate poke weed mitogen stimulated in vitro lymphocyte Ig synthesis via interference with either T4 suppressor inducer or T8 suppressor effector cells. Measurement of total and platelet specific Ig will be performed in an effort to identify regulatory defects unique to ATP lymphocytes. Gene polymorphism in the major histocompatibility class-II complex will be explored as a marker for susceptibility to develop ATP. Total genomic DNA from ATP and control patients with known HLA DR antigens will be probed with cDNA representing the DR Alpha, DR Beta, and DQ Beta chains in an effort to identify restriction fragment polymorphism which correlates with disease expression.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001821-03
Application #
3082193
Study Section
(SRC)
Project Start
1986-08-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012