# MOLECULAR BASIS FOR T LYMPHOCYTE FACTOR ACTIVITY

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1989 · $101,988

## Abstract

T lymphocytes play an integral role in both cellular and humoral immune
responses, carrying out direct effector functions such as cytolysis as well
as mediating regulatory functions via secreted lymphokines.  T cell
activation antigen can be defined only in operational terms:  development
of functional activity, lymphokine production, or proliferation.  The
antigen receptor accounts for the specificity of T cell responses.
Antigenic stimulation induces lymphokine secretion, including interleukin 2
(IL-2), and also causes an increase in the number of cell surface receptors
for IL-2 which, in turn, augments the proliferative response produced by
IL-2.  The biochemical events which follow stimulation of T cells have not
been fully characterized.  T cell responses are modulated in a variety of
ways.  IL-2 has a profound immunoregulatory effect on the cell which
produces it:  When cells which secrete IL-2 are exposed to IL-2, they
become unresponsive to antigen.  Gamma interferon acts on macrophages to
increase expression of class II major histocompatibility antigens which are
required for effective antigen presentation.  Resting macrophages secrete
apoprotein E which has profound inhibitory immunoregulatory activity; this
secretion is reduced when macrophages are stimulated.  Thus, there are
several feedback pathways that can influence T cell responses.  We intend
to characterize the cellular and biochemical processes which are associated
with activation of T lymphocytes.  In particular, we want to distinguish
between those events that are initiated by stimulation with antigen and
those that are induced by lymphokines such as IL-2.  We also intend to
characterize the processes involved in the negative regulation of T cell
responses.  In particular, we want to determine the basis for
unresponsiveness to antigen which is induced when cloned murine T cells are
exposed to IL-2.  We also want to determine the role of apoprotein-E,
produced by macrophages, in the regulation of the response of T cells.  In
these studies, we will use cloned T cells, fixed antigen-presenting cells,
monoclonal antibodies, and lymphokines produced by recombinant DNA
technology.  Thus, discriminating model systems are available for studying
the metabolic events induced by specific stimuli.

## Key facts

- **NIH application ID:** 3127652
- **Project number:** 5R01AI018061-08
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** FRANK W. FITCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $101,988
- **Award type:** 5
- **Project period:** 1982-05-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127652

## Citation

> US National Institutes of Health, RePORTER application 3127652, MOLECULAR BASIS FOR T LYMPHOCYTE FACTOR ACTIVITY (5R01AI018061-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127652. Licensed CC0.

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