At least two purine enzyme deficiencies have been associated with immunodeficiency diseases. Adenosine deaminase (ADA) deficiency is associated with severe combined immunodeficiency disease and purine nucleoside phosphorylase (PNPase) deficiency is associated with a loss of cellular immunity. Nucleosides which accumulate in these enzyme deficiencies, i.e., adenosine, deoxyadenosine, and deoxyguanosine, appear to play causal roles in the immune dysfunction. The biochemical basis for the unique sensitivity of lymphocytes (T-cells in particular) to these nucleosides is thought to be due to the presence of certain enzymes (kinases) in lymphocyte subpopulations. These enzymes """"""""salvage"""""""" the toxic nucleosides preferentially when compared to other tissues. The biochemical make-up, therefore, of a particular lymphocyte subpopulation can be anticipated to contain relatively high levels of the appropriate kinases. The proposed project will attempt to: 1) identify the T-lymphocyte subsets which are uniquely sensitive to these and other nucleosides; and 2) characterize these subsets immunologically and biochemically. The results obtained with normal and neoplastic T-cell counterparts will be compared to assess changes which may occur with malignant conversion. The long-term objective will be to identify those characteristics of lymphocytes which confer sensitivity to these nucleosides so that a rational approach to treatment of T-cell (and even, B-cell) malignancies can be devised.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD013951-05
Application #
3312390
Study Section
Immunobiology Study Section (IMB)
Project Start
1979-07-01
Project End
1987-09-30
Budget Start
1986-04-01
Budget End
1987-09-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Priebe, T; Platsoucas, C D; Seki, H et al. (1990) Purine nucleoside modulation of functions of human lymphocytes. Cell Immunol 129:321-8
Priebe, T; Ruiz, L; Nelson, J A (1990) Role of natural killer cells in the modulation of primary antibody production by purine nucleosides and their analogs. Cell Immunol 130:513-9
Priebe, T; Platsoucas, C D; Nelson, J A (1990) Adenosine receptors and modulation of natural killer cell activity by purine nucleosides. Cancer Res 50:4328-31
Priebe, T; Kandil, O; Nakic, M et al. (1988) Selective modulation of antibody response and natural killer cell activity by purine nucleoside analogues. Cancer Res 48:4799-803