# MODIFICATION OF REGULATORY T-LYMHOCYTE FUNCTION

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1988 · $178,104

## Abstract

The long-term goal of this project is to elucidate the mechanisms
by which autacoids (i.e. "local hormones") modulate T-lymphocyte
function.  We have focused our attention upon the
immunoregulatory properties of adenosine (Ado).  Ado is liberated
from hypoxic cells and in the course of inflammatory reactions.
We have previously shown that brief exposure of human T-
lymphocytes to low concentrations of Ado (1 uM) causes rapid but
selective alteration in the expression of T-cell surface antigens
(e.g. T4, T8) and receptors (Fc) and induces the activation of a
suppressor cell of T-cell dependent B-cell differentiation.  These
events are mediated by cell surface Ado receptors.  In recent
years there has been considerable progress in the characterization
of Ado receptor subtypes.  We hypothesize that Ado, acting via
specific Ado receptors, modulates the expression of cell surface
structures whose function relates directly to adenosine's ability to
alter T-lymphocyte immunoregulatory behavior.  To investigate
this hypothesis we propose to (1) determine the Ado receptor
specificity of Ado mediated immunologic events using Ado
receptor specific agonists and antagonists, (2) study the
distribution of Ado receptor subtypes on T-lymphocyte subsets
using Ado receptor specific monoclonal antibodies as well as
specific agonists and antagonists and correlate Ado receptor
distribution on T-cell subsets to their immunoregulatory function
and (3) identify cell surface antigens newly expressed on Ado
activated suppressor cells and investigate their role in Ado-
induced immunosuppression.  This will be done be developing
monoclonal antibodies to "adenosine activation antigens" (AAA).
Based upon our preliminary observations that Ado activated
suppressor cells function by limiting the availability of B-cell
growth- and differentiation factors (BCGF, BCDF) we will
investigate the specificity of these effects on BCGF and BCDF
from various sources as well as on other lymphokines and examine
the role of AAA in regulating BCGF and BCDF metabolism.  We
will also (4) identify the Ado receptors responsible for Ado
induced alterations in phospholipid and arachidonic acid
metabolism and (5) further characterize the Ado receptor
specificity, target cells and role of AAA in the phenomenon of
Ado enhancement of responses to allogeneic cells.  The adenosine
immunoregulatory system may be a physiologically important one
and study of the Ado receptor specificity of these
immunoregulatory events may ultimately lead to greater ability
to modulate specific immunoregulatory functions using Ado
receptor specific agonists and/or antagonists.

## Key facts

- **NIH application ID:** 3176459
- **Project number:** 5R01CA038353-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** STEPHEN H POLMAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $178,104
- **Award type:** 5
- **Project period:** 1984-03-01 → 1990-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176459

## Citation

> US National Institutes of Health, RePORTER application 3176459, MODIFICATION OF REGULATORY T-LYMHOCYTE FUNCTION (5R01CA038353-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3176459. Licensed CC0.

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