# PATHOGENESIS OF CHRONIC GRAFT-VS-HOST DISEASE

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1987 · $153,528

## Abstract

This work will examine the pathogenesis of chronic graft-versus-host (GVHD)
in the rat.  Bone marrow transplantation between the inbred AUG.2b (PVG)
and AUG strains is associated with the appearance of a chronic, prolonged
GVHD 4-6 months following transplantation.  These two strains are congenic
for a blood group antigen, RT2, and apparently differ for a
histocompatibility locus identical to or closely linked to RT2.  The
experiments are designed to achieve three specific aims.  The first is to
characterize the cellular and humoral immunopathological changes present in
the animals undergoing a chronic GVHD.  The onset of clinical disease
follows a period of stable chimerism and we are particularly interested in
the immunological events that occur during the onset of the GVHD.  Second,
we intend to examine the pathogenesis of the cell-mediated lesions of the
chronic GVHD by adoptive transfer, in vitro modification of the
transplanted marrow, and the generation of alloreactive T-cell clones.  The
T-cell clones will be particularly useful for reconstitution experiments to
establish the cell subpopulations and target specificity required to
produce the GVHD.  Third, the use of the congenic donor-recipient strain
combination provides the opportunity to characterize the antigen(s)
responsible for stimulating a chronic GVHD.  We intend to use donor
antihost antibody and T-cell clones to establish the tissue distribution,
degree of polymorphism and structural characteristics of the target antigen.

The importance of the proposed work is the opportunity to study an
experimental model of chronic graft-versus-host disease that closely mimics
the disease seen following bone marrow transplantation between
HLA-identical siblings.  The chronic GVHD seen in man and in our
experimental model share important clinical and pathological features that
allow for experimental investigation not possible in other experimental
animals.  The unique feature of the RT2 congenic model is a chronic GVHD in
MHC matched animals directed against a single non-MHC background gene.  The
results obtained from these studies will greatly improve our understanding
of the pathogenesis of chronic GVHD and should have direct application for
donor-recipient selections and therapeutic applications of bone marrow
transplantation in man.  (TT)

## Key facts

- **NIH application ID:** 3177119
- **Project number:** 5R01CA038804-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** DONALD V CRAMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $153,528
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177119

## Citation

> US National Institutes of Health, RePORTER application 3177119, PATHOGENESIS OF CHRONIC GRAFT-VS-HOST DISEASE (5R01CA038804-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177119. Licensed CC0.

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