# IMMUNOBIOLOGY OF HYBRID RESISTANCE

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1993 · $202,509

## Abstract

Bone marrow cell (BMC) transplantation is a successful treatment modality
for leukemia, aplastic anemia, severe combined immunodeficiency (SCID),
and even some solid tissue tumors.  Transfer of allogeneic BMC presents 3
major complications: failure to engraft or rejection, graft-versus-host
disease (GVHD) and recurrence of disease.  Depletion of T cells from the
marrow prevents serious GVHD often, but increases the likelihood for
rejection and recurrence of disease, e.g. leukemia.  T cell depleted
(TCD) BMC would be the choice if one could prevent rejection and leukemia
recurrence, since GVHD would be ameliorated.  The purpose of this
proposal is to analyze those host effector cells which prevent
engraftment, and to develop strategies to allow engraftment of TCD BMC in
a murine model.  Host NK cells recognize 'recessively inherited'
Hemopoietic histocompatibility (Hh-1) antigens on stem cells, the basis
of Fl hybrid resistance to BMC grafts.  Host CD8+ T cells recognize class
I antigens on donor stem cells.  Specific Aims: 1. Characterize NK cells
which recognize specific Hh-1 antigens specifically.  Clone the genes for
the NK markers 5E6 and 1OA7 associated with the specific rejection of BMC
expressing Hh-1 determinants 2 and 5, respectively.  Produce transgenic
mice to test the idea that 5E6 and/or 1OA7 are specific NK receptors. 2.
Analyze the mechanisms by which TCD BMC are more sensitive to rejection
and develop strategies to allow growth without causing GVHD.  Test the
ideas i) myeloid stem cells are rejected by NK cells or by newly
sensitized T cells; ii) donor T cells inhibit host effectors; and iii)
host T cells reject those donor T cells.  Characterize marrow T cell
after separation from stem cells by counter current elutriation, a
technique used clinically to prevent GVHD.  Determine the nature of the
host T cell that rejects donor T cells by cell transfer studies involving
T cell-deprived SCID host mice. 3. Develop an in vitro assay for BMC
rejection to allow better evaluation of these immune cell interactions.
This work may provide data relevant to clinical BMC transplantation.

## Key facts

- **NIH application ID:** 3174584
- **Project number:** 2R01CA036922-10
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** Michael Bennett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $202,509
- **Award type:** 2
- **Project period:** 1984-03-01 → 1998-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174584

## Citation

> US National Institutes of Health, RePORTER application 3174584, IMMUNOBIOLOGY OF HYBRID RESISTANCE (2R01CA036922-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174584. Licensed CC0.

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