# 1L-2 AND ITS RECEPTOR IN THE PATHOGENESIS OF

> **NIH NIH R01** · STANFORD UNIVERSITY · 1987 · $123,698

## Abstract

Recent evidence indicates that cells become malignant when the normal
control mechanisms over cell division and proliferation malfunction. The
purpose of the studies described in this proposal will be to obtain a
better understanding of the mechanisms used by IL-2 and its receptor to
promote T-cell proliferation and to define possible sites at which this
process may malfunction in malignancy.  Normal T-cell growth and clonal
proliferation probably occur by an autocrine pathway in which the cell both
makes and responds to its own growth factor.  Normally induction of IL-2
and its receptor is controlled by the presence of antigen; thus T-cell
growth is limited to a subpopulation of antigen-specific cells.  However,
the autocrine nature of this process suggests that it requires delicate
regulation, and we hypothesize that perturbations of the control mechanisms
over IL-2 or its receptor may produce a transformed cell.

To test this hypothesis we plan to introduce the gene for IL-2 into the
IL-2 dependent cell lines CT-6 and CTLL, which constitutively make the IL-2
receptor but not IL-2.  If these cells become IL-2 independent, as our
preliminary studies indicate, we will test for a transformed phenotype by
injecting the cells into mice of a genetic background which is identical to
that of the cell line.  If tumors cannot be established or if the cells
cannot be made to become IL-2 independent, we will change the regulatory
regions of the gene to bring it under constitutive control, and determine
if the modified gene is capable of conferring the malignant phenotype.

In addition we plan to investigate the generality of the growth-promoting
properties of the IL-2 receptor by introducing the IL-2 receptor gene into
a variety of non-T lymphocytes and other cells and testing for the ability
of IL-2 to promote proliferation of the cells receiving the gene.

Finally, we will examine the role of the IL-2 receptor in the proliferation
of human T-cell lymphomas which express the IL-2 receptor constitutively.
We will test the effect of a plasmid producing an anti-sense copy of the
IL-2 receptor mRNA on the growth of a HTLV infected cell line which
constitutively makes the IL-2 receptor.  We will also examine the function
of this isolated receptor gene.

We anticipate that these studies will help determine if IL-2 or the IL-2
receptor have a role in the pathogenesis of human T-cell malignancies.

## Key facts

- **NIH application ID:** 3178798
- **Project number:** 5R01CA039612-03
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** Gerald R. Crabtree
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $123,698
- **Award type:** 5
- **Project period:** 1985-05-01 → 1988-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178798

## Citation

> US National Institutes of Health, RePORTER application 3178798, 1L-2 AND ITS RECEPTOR IN THE PATHOGENESIS OF (5R01CA039612-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178798. Licensed CC0.

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