# NEW APPROACH TO THE REGULATION OF HUMAN T CELL FUNCTION

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1990 · $160,835

## Abstract

This proposal involves the study of biochemical mechanisms and
purine metabolizing enzymes involved in purine nucleoside
phosphorylase (PNP) deficiency and a comprehensive
immunological and biochemical study of canine models of induced
PNP deficiency.  The distribution of deoxynucleoside kinases in
isolated lymphocytes will be determined by autoradiography and
catalytic assay and the kinetics of phosphorylation of
deoxyguanosine by purified enzymes.  Mechanisms including
catabolism of nucleotides, inosine mediated inhibition of T cell
function and intracellular cyclic nucleotides will be studied.  We
will investigate in vitro the proliferation and metabolism of
deoxyguanosine in isolated dog, rat, and human lymphocyte sub-
populations.  We will determine if 8-aminoguanosine is a specific
PNP inhibitor.  We will study the immunosuppression produced by
8-aminoguanosine treatment in three model canine systems:  the
prevention of platelet immunization to allogeneic platelet
transfusions; the prolongation of skin graft survival in dogs
receiving grafts from DLA nonidentical unrelated donor dogs; the
prevention of graft-versus-host disease in allogeneic bone marrow
transplantation.  In these studies the phenotypic characterization
of B and T cells and T cell subsets will be assayed by specific
monoclonal antibodies.  Immunological responses in vivo will be
monitored by immunization with sheep red blood cells and keyhole
limpet hemocyanin, and in vitro by mitogen stimulation and mixed
leukocyte culture.  To monitor the efficacy of PNP inhibition we
will use HPLC to assay the bioactive inhibitor 8-aminoguanine and
purine metabolites in plasma, and nucleotides in red and white
cells.  This research provides a novel approach to the specific
regulation of T cell function; the results may be directly
applicable to platelet transfusion therapy in the support of cancer
patients, and may benefit organ and marrow transplantation and
treatment of T cell malignancies.

## Key facts

- **NIH application ID:** 3128888
- **Project number:** 5R01AI019565-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** WILLIAM R OSBORNE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $160,835
- **Award type:** 5
- **Project period:** 1983-09-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128888

## Citation

> US National Institutes of Health, RePORTER application 3128888, NEW APPROACH TO THE REGULATION OF HUMAN T CELL FUNCTION (5R01AI019565-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128888. Licensed CC0.

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