# SUPPRESSOR T CELL PATHWAYS IN T CELL TOLERANCE

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1989 · $187,495

## Abstract

We propose to continue our investigation of the inductive events and
suppressor T cell/T cell factor (Ts/TsF)-mediated regulation of
delayed-type hypersensitivity (DTH) responses to 2,4-dinitrofluorobenzene
(DNFB).  As precise analysis of the induction and effector mechanisms of
complex inductive and regulatory circuits is possible only via the use of
cells and factors from cloned T cell lines and hybridomas, particular
emphasis will be given to the isolation and characterization of clonal
sources of regulatory Ts/TsF and clonal sources of potential targets of
these regulatory cells.  Studies on the inductive events of DTH will focus
on further characterization, on both the population and clonal levels, of
the hapten-specific, MHC Class II-restricted T cell subsets involved in
this process [helper T cells for DTH (Thdh), proliferative T cells (Tprlf),
and precursor DTH effector cells (pTDH)].  Studies on the inductive and
effector events of antigen-specific Ts circuits induced by the intravenous
injection of syngeneic DNP-modified spleen cells (DNP-SP) will focus on
several areas.  The role of L3T4+ Ts-inducer (Ts-i) cells in the Ts circuit
will be probed using in vivo injection of monoclonal GK1.5 antibody
(directed against the MHC Class II T cell receptor-associated L3T4a
determinant) and by examining the suppressive mechanisms  of our recently
described L3T4+ Ts-i clones.  The mechanisms and cellular targets of
efferent (elicitation phase) and afferent (induction phase)-acting Ts-1 and
Ts-2 effector cells will be investigated using both polyclonal and clonal
sources of these cells and their targets.  Lastly, major emphasis will be
placed on investigation of the biochemistry, receptor genes, and molecular
mechanisms of effector suppression using a monoclonal, DNP-specific,
efferent-acting TsF (Clone 26.10.2) as a probe.  Studies are proposed
wherein genetic and molecular mechanisms of the divergent pathways by which
this monoclonal TsF appears to mediate suppression will be examined - a)
directly and specifically on DTH-effector TDH cells; b) indirectly via
triggering of a nonspecific factor from antigen-primed Ts-auxiliary cells;
and, c) via induction of second-order Ts.  We feel that the past experience
of our laboratory in the study of DTH immunoregulation and our recently
developed technology for producing clonal sources of both DTH effector and
Ts cells make these goals attainable.  Understanding of Ts/TsF regulation
of DTH responses gained by these studies should prove valuable for our
future ability to manipulate the immune system for both the prevention and
treatment of neoplasia and human immunoregulatory disease.

## Key facts

- **NIH application ID:** 3128153
- **Project number:** 5R01AI018755-08
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** STEPHEN D MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $187,495
- **Award type:** 5
- **Project period:** 1981-08-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128153

## Citation

> US National Institutes of Health, RePORTER application 3128153, SUPPRESSOR T CELL PATHWAYS IN T CELL TOLERANCE (5R01AI018755-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128153. Licensed CC0.

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