# PURINE METABOLISM AND HUMAN LYMPHOCYTE MATURATION

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1987 · $149,509

## Abstract

The purpose of the proposed research is to gain knowledge regarding the
function of the ecto enzyme, 5 prime-nucleotidase (ecto-5 prime-NT) on
human B and T cells.  The proposal is divided into three related projects.

First, we will develop methods to separate ecto-5 prime-NT+ from ecto-5
prime-NT- lymphocytes.  A monoclonal antibody will be produced after
immunization of mice with 5 prime-NT purified from human placenta.  Using
anti-ecto-5 prime-NT antibodies, human peripheral T and B cells will be
separated into ecto-5 prime-NT+ and ecto-5 prime-NT- populations by cell
sorting, panning, complement mediated lysis of ecto-5 prime-NT+ cells,
and/or rosetting.

In the second project, we will conduct basic studies of purine metabolism
in ecto-5  prime-NT+ and ecto-5 prime-NT-T cells.  The ability of these two
populations to proliferate in response to mitogens will be compared in
purine-free medium (in which the cells must meet their purine requirements
by de novo synthesis), in medium supplemented with hypoxathine (which can
meet all purine requirements via salvage), and in medium supplemented with
inosine 5 prime-monophosphate (which can meet all purine requirements via
salvage only after conversion to inosine by ecto-5 prime-NT).  We will
learn whether the presence or absence of ecto-5 prime-NT activity
influences the routes by which human T cells meet their purine requirements
and whether ecto-5 prime-NT lymphocytes might have a selective advantage
over ecto-5 prime-NT-lymphocytes in specific microenvironments such as the
thymus and bone marrow where there is considerable cell death and purines
might be salvaged from exogenous nucleotides.

Finally, we will compare the functional capabilities of ecto-5 prime-NT+
vs. ecto-5-NT-T and B cells.  The results of these experiments in
combination with those of the second project will reveal whether specifc
patterns of purine metabolism are adapted for specific types of lymphocyte
functions; i.e., those which require proliferation as compared to those
which do not.  The purified populations will also be characterized for the
co-expression of other cell surface antigens using commercially available
monoclonal antibodies to determine whether the expression of ecto-5
prime-NT activity, in conjunction with other cell surface markers, can be
used to define functional subsets of human T and B lymphocytes.  Our goal
is to understand the significance of the reduced numbers of ecto-5
prime-NT+ lymphocytes (and increased numbers of ecto-5 prime-NT-
lymphocytes) in patients with immunodeficiency diseases.

## Key facts

- **NIH application ID:** 3127760
- **Project number:** 5R01AI018220-06
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** Linda F Thompson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $149,509
- **Award type:** 5
- **Project period:** 1981-08-01 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127760

## Citation

> US National Institutes of Health, RePORTER application 3127760, PURINE METABOLISM AND HUMAN LYMPHOCYTE MATURATION (5R01AI018220-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127760. Licensed CC0.

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