# ETIOLOGY & PATHOGENESIS OF MURINE GRAFT VS HOST DISEASE

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1991 · $189,474

## Abstract

Clinical bone marrow transplantation is an important therapeutic treatment
for several diseases including high risk leukemia, aplastic anemia, and
severe combined immunodeficiency.  In addition there is a wide range of
metabolic and genetic disorders that can potentially be corrected by this
approach.  Recently, based on preliminary data, it has also been suggested
that marrow transplantation may be a very effective tool in acquired
immunodeficiency syndrome (AIDS) therapy.  However, the usefulness of
marrow transplantation is currently limited by several important risk
factors, the principal one being graft-versus-host disease (GVHD), an
oftentimes lethal complication which occurs in a high proportion of
transplants.  The general aim of this proposal is to continue our study of
the immunobiology of lethal GVHD in murine models.  In recent years we have
clearly defined the relative etiological roles of both CD4+ and CD8+ T cell
subsets in GVHD directed across both major histocompatibility complex (MHC)
(class I and II) and non-MHC (multiple minor H) genetic barriers.  We now
intend to focus on the characteristics of GVHD pathogenesis mediated by
each of these subsets and to define involved mechanisms, particularly
across multiple minor H antigen differences.  In this regard we will
concentrate our efforts specifically on the following areas: 1) the
features of T cell subsets mediating GVHD directed to minor H antigens
including the functional characteristics and related differences in
pathogenesis of the T cell subsets involved, the tissue expression of minor
H antigens and recognition sites for T cell subsets, and the role of tumor
necrosis factor (TNF) in development of GVHD; (2) the role of
immunodominance in GVHD responses to multiple minor H antigens by which
responses are directed to only a few select antigens, why in vivo results
differ from in vitro, tissue distribution of minor H antigens, and
mechanisms of immunodominance; and (3) the use of selective CD8+ T cell
depletion of allogeneic donor inoculum to avoid GVHD directed to minor H
antigens in irradiated recipients and allow for either enhanced resistance
to cytomegalovirus (CMV) challenge or graft-versus-leukemia effects.  In
all, we feel that the projects designed in this proposal will add
significant understanding to the mechanism and pathogenesis of GVHD as
mediated by T cell subsets in MHC-matched transplantation situations.
Insights generated from these studies will hopefully lead to new approaches
for overcoming some of the major obstacles for improved and expanded use of
clinical bone marrow transplantation.

## Key facts

- **NIH application ID:** 3177473
- **Project number:** 2R01CA038951-08
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** Robert Korngold
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $189,474
- **Award type:** 2
- **Project period:** 1988-01-01 → 1993-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177473

## Citation

> US National Institutes of Health, RePORTER application 3177473, ETIOLOGY & PATHOGENESIS OF MURINE GRAFT VS HOST DISEASE (2R01CA038951-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177473. Licensed CC0.

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