# MECHANISM OF BONE MARROW GRAFT REJECTION

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1992 · $226,741

## Abstract

The objective of this proposal is to understand the mechanisms
that are responsible for marrow graft rejection in the mouse.
Previous studies had shown that the acute rejection of allogeneic
marrow grafts is due to natural killer cells which acquire in vivo
specificity by making use of antibody that induces them to reject
marrow.  Since this mechanism does not explain all known
phenomena in marrow graft rejection it is the objective of this
proposal to uncover the not yet discovered mechanisms that play
a role in marrow graft rejection.  The first aim of this proposal is
to characterize the cell surface phenotype of a new type of cell
that we have identified to be responsible for acute rejection of
allogeneic marrow grafts.  We will use an adoptive transfer assay
from responder to nonresponder mice in combination with
antibody treatment to identify this cells.  The second aim is to
understand the relationship of acute and delayed graft rejection in
an attempt to find out whether both mechanisms share the same
specificities and effector cells.  Using in vitro cytotoxicity assays
and in vivo competition assays attempts will be made to
determine the fine specificity of the effector cells responsible for
acute and delayed rejection.  In approaches very similar to those
used to characterize the cells responsible for allogeneic marrow
graft rejection we will investigate and try to isolate the cell
responsible for hybrid resistance.  Cell lines of both types of cells
will be established and attempts will be made to clone these cells
in lymphokine containing media.  We will study the mode of action
of these cells in both in vivo and in vitro assays.  Biochemical
procedures will be used to explore whether these cells express T
cell receptors and if not attempts will be made to find out what
the nature of their receptors may be.  Since the hybrid resistance
effector mechanism appears to express autoreactive potential we
will test the hypothesis that the hybrid resistance cell is involved
in the induction of autoimmunity.  To do this F1 hybrid mice will
be transplanted with marrow to stimulate the hybrid resistance
effector mechanism and the production of autoantibody will be
assessed.

## Key facts

- **NIH application ID:** 3175520
- **Project number:** 5R01CA037706-08
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** GUNTHER DENNERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $226,741
- **Award type:** 5
- **Project period:** 1984-07-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175520

## Citation

> US National Institutes of Health, RePORTER application 3175520, MECHANISM OF BONE MARROW GRAFT REJECTION (5R01CA037706-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175520. Licensed CC0.

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