# T-CELL SUBPOPULATION IN TRANSPLANTATION IMMUNITY

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1992 · $455,330

## Abstract

Eta-1 is a single copy gene encoding a 60 kD glycoprotein secreted by
activated T-cells.  Studies indicate the Eta-1 gene maps to a locus that
confers genetic resistance to lethal infection by intracellular bacterial
parasites.  Inbred mouse strains bearing the Eta-1a allele display strong
and rapid Eta-1 responses after bacterial infection and are resistant to
intracellular bacterial growth.  Conversely, inbred strains that carry the
b allele exhibit delayed and reduced Eta-1 responses and are unable to
contain bacterial growth.  Studies of the cellular mechanism of genetic
resistance conferred by Eta-1 suggest that binding of the Eta-1 protein to
specific receptors on macrophages may be responsible for resistance.  A
second area of study comes from examination of cell surface events and
intracellular signalling pathways that lead to cytokine expression in CD4+
T-cells after stimulation by bacterial and retroviral superantigens.
Analysis of cytokine gene expression after T-cell activation by the two
types of ligand indicates that a putative Ca2+-independent activation
pathway triggered by superantigen leads to expression of the Eta-1 gene but
not IFN-gamma, IL-2 or IL-3 expression.  By contrast, triggering of the
same clone by conventional peptide-I-A complexes results in strong
induction of all of these cytokines.  The proposed studies will further
define and distinguish the activation pathway triggered by superantigen
resulting in selective Eta-1 gene expression from the pathway coupled to
TCR ligation by conventional peptide I-A complexes.  A third are of study
comes from the identification of an example of dysregulated Eta-1
expression.  We screened a panel of inbred mouse strains that develop
different types of autoimmune disorders for evidence of elevated levels of
constitutive Eta-1 expression.  We found that MRL/1pr mice display a
selective and substantial elevation of Eta-1 gene expression.  Further
studies of the interaction between Eta-1 and B-cells indicate that this
cytokine promotes IgM and IgG production.  These observations open the
possibility that dysregulated Eta-1 expression may be responsible for
polyclonal B-cell activation, the hallmark of this form of murine lupus.
These findings also suggest that a subset of the autoimmune diseases may be
marked by dysregulated expression of Eta-1 and thus represent a discreet
nosologic entity within the autoimmune disease spectrum.  If so, treatment
of this biochemical disorder may be directed at correction of Eta-1
overexpression rather than current approaches which employ non-specific
immunosuppressive agents.

## Key facts

- **NIH application ID:** 3125119
- **Project number:** 2R01AI012184-17
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** HARVEY CANTOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $455,330
- **Award type:** 2
- **Project period:** 1977-07-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125119

## Citation

> US National Institutes of Health, RePORTER application 3125119, T-CELL SUBPOPULATION IN TRANSPLANTATION IMMUNITY (2R01AI012184-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125119. Licensed CC0.

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