# NUTRITIONAL EFFECT OF NUCLEOTIDES ON LYMPHOCYTE

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 1988 · $188,737

## Abstract

Studies from our laboratories have demonstrated a requirement for a source
of preformed purine and/or pyrimidine bases for maintenance of cellular
immunity.  A nucleotide-free diet (NFD) delays rejection of H2-incompatible
murine cardiac allografts, and suppresses lymphocyte proliferation to
alloantigens.  NFD acts synergistically with cyclosporine in suppression of
allograft rejection.  It slows development of graft versus host disease,
decreases interleukin-2 production, suppresses induction of phenotypic
T-helper cell populations, and increases suppressor cell activity.  Mice
maintained on NFD are more susceptible to S. aureus and C. albicans
infections.  Our results indicate that the T-helper cell population is the
most affected.  T-cell tumors also show this dependence upon exogenous
purine and/or pyrimidines.  Enzyme and function studies in NFD fed hosts
suggest delay in lymphocyte maturation in the G1 phase of the cell cycle.
This maturation arrest is similar to that observed with various
immunosuppressive agents, including cyclosporine.  To dissect the mechanism
by which these substrates exert this influence, we propose the following
experiments:  1) To determine the effect of dietary nucleotides on
lymphokine (IL-3, Gamma-IFN) and monokine (IL-1) production and upon IL-2
responsiveness; 2) to determine in vitro the specific purine or pyrimidine
requirements of T-helper and T-cytotoxic cell clones; 3) to determine the
synergism of cyclosporine with specific purines or pyrimidines upon helper
or cytotoxic clone function; 4) to determine the influence of dietary
nucleotides on phagocytic cell function (O-2 generation, lysosomal enzyme
activity, macrophage mobility); 5) to determine dose response curves of
specific purines or pyrimidines to immune responses measured in vivo
(PLN,DCH, allograft rejection) or in vitro (MLC, lectin); the minimum
period of acclimatization to NFD to exert an immunosuppressive response
will also be examined; 6) to determine the influence of NFD in combination
with blood transfusion and cyclosporine in a vascularized heterotopic heart
transplant model; and 7) to examine the possible synergism of NFD with
chemotherapeutic anti-metabolites in the treatment of T-cell lymphomas.  By
clarifying both the mechanism by which NFD suppresses cellular immunity and
host defenses and by defining the specific dose of pyrimidines or purines
which will maintain immunity, these studies should define dietary regimens
which will better support the host defenses of critically ill patients.

## Key facts

- **NIH application ID:** 3173065
- **Project number:** 5R01CA035492-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **SAM.gov UEI:** ZUFBNVZ587D4
- **Principal Investigator:** CHARLES T VAN BUREN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $188,737
- **Award type:** 5
- **Project period:** 1987-03-20 → 1990-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173065

## Citation

> US National Institutes of Health, RePORTER application 3173065, NUTRITIONAL EFFECT OF NUCLEOTIDES ON LYMPHOCYTE (5R01CA035492-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173065. Licensed CC0.

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