# CONTROL OF GRAFT VERSUS HOST DISEASE

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 1988 · $124,115

## Abstract

Acute and chronic graft versus host disease (GVHD) are a major limitation
to the increased use of human allogeneic bone marrow transplantation.  We
have established a murine model of acute and chronic GVHD due to non-major
histocompatibility antigens (non-H-2 antigens) which includes many features
of human GVHD including scleroderma skin changes and immunodeficiency.  Our
purpose is to define the cellular mechanisms of acute and chronic GVHD
particularly as they relate to human clinical transplantation.
Histopathologically acute GVHD is characterized by the cytolytic
destruction of recipient cells while chronic GVHD is due to increased
collagen deposition.  T lymphocytes from mice with acute and chronic GVHD
will be clonally analysed to determine the relative frequency of recipient
specific CTL, helper T lymphocytes that stimulate fibroblast collagen
production and T lymphocytes with specificity for autologous Ia antigen
(autoreactive T lymphocytes).  The antigenic specificity of the cloned T
lymphocytes will determine in both blastogenic and cytolytic assays using
recombinant mice.  The role of antigenic dose in the pathogenesis of GVHD
will be studied by using strain combinations that differ at 3 or less
non-H-2 antigens.  The combination, B10.D2-BALB/c, in which bidirectional
GVHD does not occur will be studied to determine if the lack of reciprocal
GVHD is due to immunological or environmental factors.  The collagen
produced by the in vitro stimulation of cultured fibroblasts will be
compared to in vivo collagen from mice with de novo chronic GVHD by
determining the Type I/III collagen ratio.  Since the in vitro lysis of
lymphoid targets may be a poor model for in vivo GVHD, non-lymphoid targets
(fibroblasts, keratinocytes) will be evaluated.  The role of autologous Ia
antigen expression in the pathogenesis of acute and chronic GVHD will be
investigated by using Ia positive and negative non-lymphoid targets.  The
role of natural suppressor cells and autoreactive T lymphocytes in the
pathogenesis of post-transplant immunodeficiency and immune dysregulation
will be studied.  In summary, this grant uses a murine model of non-H-2
GVHD to increase our understanding of human GVHD.  The questions selected
for study are those that have clinical relevance.

## Key facts

- **NIH application ID:** 3173482
- **Project number:** 5R01CA035971-05
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **SAM.gov UEI:** DVL1CMRMWRN9
- **Principal Investigator:** Robertson Parkman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $124,115
- **Award type:** 5
- **Project period:** 1982-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173482

## Citation

> US National Institutes of Health, RePORTER application 3173482, CONTROL OF GRAFT VERSUS HOST DISEASE (5R01CA035971-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173482. Licensed CC0.

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