# ETIOLOGY AND PATHOGENESIS OF MURINE GRAFT VS HOST DISEAS

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1987 · $74,350

## Abstract

Bone marrow transplantation is an important clinical procedure for the cure
of such diseases as aplastic anemia, leukemia, and severe combined
immunodeficiency.  Its potential application for numerous other hematologic
disorders is obvious, if the risk factors associated with the technique
could be significantly reduced.  In this regard, the major complication
developing after marrow transfer is graft-versus-host disease (GVHD), which
occurs when there is a genetic histoincompatibility between the marrow
donor and recipient.  Mature T cells contaminating the donor marrow
inoculum were first shown to be the cause of the disease in animal models
and since then have been strongly implicated as the cause in man.  However,
the etiological role of particular T-cell subsets (helper or cytotoxic) and
the mechanisms that are involved in the pathogenesis of GVHD are still
obscure.  Murine models for GVHD have been chosen to study these questions,
largely because of the availability of both genetically well-defined inbred
strains and reagents for characterizing lymphoid subpopulations.
Preliminary data in these models suggest that different T-cell subsets may
be responsible for GVHD when directed to either non-MHC, class I, or class
II MHC-type antigens, i.e., Lyt 2+ cells appear to be involved in
anti-minor H and H-2K GVHD whereas Lyt 1+2-\cells may be responsible for
anti-full MHC or I region GVHD.  Our principal aim is to clearly define the
participation of these T-cell subsets in GVHD across various genetic
barriers. This will be approached by both negative and positive selection
techniques of cell subsets in donor inoculum and by sequential
histopathologic examination of mice undergoing GVHD.  Models for two other
major sources of complication in bone marrow transplantation, that of
immunodeficiency associated with GVHD and host-versus-marrow graft
rejection, will also be investigated.  Focus will be placed on the lack of
CTL antiviral responses in mice with ongoing GVHD and the cause of host
resistance across a non-MHC genetic barrier.  The projects presented in
this proposal should add significant basic understanding of these major
obstacles to clinical marrow transplantation and provide new insights
towards possible approaches to surmount them.  (TT)

## Key facts

- **NIH application ID:** 3177482
- **Project number:** 7R01CA038951-04
- **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:** 1987
- **Award amount:** $74,350
- **Award type:** 7
- **Project period:** 1987-08-01 → 1987-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177482

## Citation

> US National Institutes of Health, RePORTER application 3177482, ETIOLOGY AND PATHOGENESIS OF MURINE GRAFT VS HOST DISEAS (7R01CA038951-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177482. Licensed CC0.

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