Inherited deficiencies in man of the enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been found to be associated with patients having severe combined immunodeficiency disease (SCID) and a T cell deficiency, respectively. These specific immunodeficiencies are thought to arise from blocks in lymphocyte differentiation caused by the effects of the specific enzyme deficiency. However, little is known about the state or stages of lymphocyte development which are affected by the enzyme deficiency nor is it known what biochemical mechanisms are responsible for the selective pathogenicity of the immune system. The major objectives of this proposal are to identify in the normal rat lymphoid system and in the regenerating lymphoid system after irradiation what cell populations within the rat T and B lymphocyte developmental lineage are preferentially affected by an induced adenosine deaminase deficiency. In vitro correlative studies will also be performed using fetal organ cultures and rat leukemic cell culture lines representing differing stages of differentiation. Once having identified the sensitive populations we will isolate and compare sensitive and insensitive in vivo and in vitro lymphoid populations for various enzymatic and metabolic characteristics which are potentially responsible for the selective pathogenicity of the immune system.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Modified Research Career Development Award (K04)
Project #
5K04HD000554-02
Application #
3073129
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1984-04-01
Project End
1985-12-31
Budget Start
1985-04-01
Budget End
1985-12-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
Osborne, W R; Barton, R W (1986) A rat model of purine nucleoside phosphorylase deficiency. Immunology 59:63-7
Barton, R W; Osborne, W R (1986) The effects of PNP inhibition on rat lymphoid cell populations. Adv Exp Med Biol 195 Pt B:429-35
Barton, R W (1985) The effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat. Cell Immunol 95:297-310