# IMMUOREGULATORY MECHANISMS IN THE RHEUMATIC DISEASES

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1990 · $186,868

## Abstract

Our long term objective has been to elucidate the immunologic mechanisms
which are important in the pathogenesis of the autoimmune connective tissue
diseases.  We have recently made the novel observation that CD8+ lymphocyte
subsets from SLE patients paradoxically sustain antibody production.  In
the next project period, we will determine whether these CD8+ cells found
in normal subjects.  We will learn whether these cells provide help for B
cell activation or are limited to amplifying antibody production by fully
differentiated B cells.  Using lymphocytes from normal individuals, we will
test the hypothesis that up-regulatory effects on antibody production by
CD8+ cells reflect an intermediate maturation phase of these cells.  This
will be accomplished by activating individual CD8+ with monoclonal
antibodies against cell surface receptors and determining the conditions
which enable them to enhance or suppress antibody production.  Signal
transduction pathways involved in the generation of regulatory activities
will be documented.  We will study mobilization of intracellular free
calcium and ligand specific activation of protein kinase gained from the
study of normal lymphocytes, we will perform comparative studies of CD8+
lymphocytes from SLE patients, family members, discordant twin pairs and
normals to determine whether SLE cells are more prone to become amplifiers
instead of suppressors.  Alternatively, we will determine whether excessive
B cell help and impaired suppressor activity result from a deficiency of
signals from other cells which are required for the terminal
differentiation of CD8+ cells.  Elucidation of the specific signals which
induce suppression or enhancement and the biochemical mechanisms leading to
their regulatory effects in SLE will be most useful in our understanding of
the pathogenesis of other chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 3155706
- **Project number:** 2R01AR029846-09A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** DAVID A HORWITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $186,868
- **Award type:** 2
- **Project period:** 1980-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155706

## Citation

> US National Institutes of Health, RePORTER application 3155706, IMMUOREGULATORY MECHANISMS IN THE RHEUMATIC DISEASES (2R01AR029846-09A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155706. Licensed CC0.

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