# REGULATION OF ACTIVITY IN CLONED ANTI-TUMOR LYMPHOCYTES

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1988 · $115,809

## Abstract

This proposal focuses on the regulation of the growth and function of
cloned antitumor lymphocytes.  The experiments over the last three years
have demonstrated that lytic activity of a population of cells varies over
a continuum of lytic efficiency at the level of individual cells rather
than by alteration of the ratio of highly lytic/non lytic cells.  The only
soluble factor necessary for the regulation of an individual cell's lytic
capacity is interleukin 2 (IL-2).  The mechanism of IL-2 regulation appears
to be through a general stimulation of protein synthesis rather than
through the selective regulation of relevant genes.  In addition we have
found evidence for the differential regulation of lymphocyte sub classes by
different lymphokines.  We will pursure these studies with clonal models of
different lymphocyte sub classes.  In addition we will pursue similar
studies with selected normal lymphocytes at different states of activation.

Based on experiments with clones that cross react with multiple antigens we
have developed a model for the differential regulation of growth and lytic
responses by the avidity of the interaction between the CTL and an antigen
bearing cell.  Thus a weak interaction is optimal for stimulation of
proliferation while stronger interactions are optimal for the stimulation
of a lytic response.  This differential regulation of responses allows for
antigen presentation by weak antigenic species within the lymphoid system
and limits lytic activity to the tumor, infection or graft site.  In
addition factors such as interferon that regulate class I antigen
expression on the target cell produce an increased effectiveness of the
lytic process at the anatomical site of attack.

Finally we demonstrate that the antigen specific interaction can have a
negative as well as a positive influence on CTL growth.  This negative
effect appears to be a direct effect on the responding cell itself rather
than a secondary effect of soluble agents.  The negative effect on growth
is through an antigen-induced non responsiveness to IL-2.  An understanding
of the mechanism of an antigen induced block in proliferation may yield
important information about the nature of one form of the induction of
tolerance.

## Key facts

- **NIH application ID:** 3172646
- **Project number:** 5R01CA034817-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** John H Russell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $115,809
- **Award type:** 5
- **Project period:** 1983-05-01 → 1990-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172646

## Citation

> US National Institutes of Health, RePORTER application 3172646, REGULATION OF ACTIVITY IN CLONED ANTI-TUMOR LYMPHOCYTES (5R01CA034817-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172646. Licensed CC0.

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