# ETIOLOGY & PATHOGENESIS OF MURINE GRAFT VS. HOST DISEASE

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1988 · $152,929

## Abstract

Clinical bone marrow transplantation has become an important
therapeutic treatment for several diseases including high risk
leukemia, aplastic anemia, and severe combined immunodeficiency.
However, graft-versus-host disease (GVHD) remains a major
complication following 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 Lyt-2+
and L3T4+ T cell subsets in GVHD directed across both 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.  In this regard we will concentrate our efforts
specifically on the following areas:  (1) the role of individual
T cell subsets in the etiology and pathogenesis of GVHD across
class I and class II MHC genetic barriers with emphasis on the
functional activity and related differences in development of GVHD
mediated by either Lyt-2+ or L3T4+ cells, the importance of target
tissue expression of MHC antigens in development of GVHD, and the
effect of non-MHC background genes on the GVHD potential of T cell
subsets: (2) the features of T cell subsets mediating GVHD directed
to minor H antigens including the role of exogenous  "help"  GVHD
mediated by purified Lyt-Z+ T cells, the functional characteristics
and related differences in pathogenesis of T cell subsets Involved
in anti-minor H GVHD, the value of in vitro assays for predicting
L3T4+ cell  GVHD potential, the importance of target tissue
expression of minor H antigens for development of GVHD, the ability
of single minor H antigens to induce lethal GVHD, and the role of
immunodominance in GVHD responses to multiple minor H antigens; (3)
the use of selective Lyt-2+ T cell depletion of allogeneic donor
inoculum to avoid GVHD directed to minor H antigens in irradiated
recipients and allow for graft-versus-leukemia effects to be
mediated by remaining donor L3T4+ cells; and (4) the use of
selective Lyt-2+ T cell depletion of allogeneic donor inoculum to
avoid GVHD directed to minor H antigens and allow for protection
of recipients to infectious virus challenge by presensitized donor
L3T4+ T and B cells.

## Key facts

- **NIH application ID:** 3177472
- **Project number:** 2R01CA038951-05
- **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:** 1988
- **Award amount:** $152,929
- **Award type:** 2
- **Project period:** 1987-08-01 → 1990-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177472

## Citation

> US National Institutes of Health, RePORTER application 3177472, ETIOLOGY & PATHOGENESIS OF MURINE GRAFT VS. HOST DISEASE (2R01CA038951-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177472. Licensed CC0.

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