# IMMUNOSUPPRESSION IN MYCOBACTERIAL DISEASES

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1991 · $232,288

## Abstract

The long-term objectives of this proposal are to elucidate
immunosuppressive mechanisms operant in human pulmonary tuberculosis.  The
previous observations and preliminary data supported by AI-18471 support
the following hypothesis:  Discrete mycobacterial protein constituents
selectively stimulate monocytes or alveolar macrophages to express
cytokines involved in inflammation, immune induction and fibrosis
(interleukin-1(IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF)]
and potential mediators of immunosuppression [interleukin-2 receptor (IL-
2R), transforming growth factor-B1 (TGF-B1)].  The increased response of
monocytes from patients with tuberculosis to such microbial factors in the
initiating event in antigen-specific suppression.  CD16 and Fc-gamma
suppressor lymphocytes stimulated by mediators produced by monocytes, and
by PPD, represent an efferent component of specific immunoregulatory
circuits as they suppress responses of CD4 lymphocytes.

The specific aims to test the hypothesis are:

1)  To characterize mycobacterial protein constituents which stimulate
monocytes and alveolar macrophages to express proinflammatory cytokines
(IL-1, IL-6, TNF) and IL-2R and to assess their induction of TGF-B1.

2)  To identify the products of mycobacterial antigen-stimulated monocytes
from patients with tuberculosis which suppress T-cell responsiveness; and

3)  To enumerate and expand potentially suppressive lymphocyte
subpopulations (CD16, Fc-gamma, gamma-delta T-cells) into cell lines and
clones, and to assess their activation by products of monocytes, and
mycobacterial constituents, and their suppression of CD4 responses.

The experimental design uses the approaches of cellular immunology,
immunochemistry, biochemistry and molecular biology.  This is a health-
related project.

## Key facts

- **NIH application ID:** 3127976
- **Project number:** 5R01AI018471-09
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** Jerrold J. Ellner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $232,288
- **Award type:** 5
- **Project period:** 1982-01-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127976

## Citation

> US National Institutes of Health, RePORTER application 3127976, IMMUNOSUPPRESSION IN MYCOBACTERIAL DISEASES (5R01AI018471-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127976. Licensed CC0.

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