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Protection from lethal graft-vs.-host disease by donor stem cell repopulation
L Rozendaal1, S T Pals, C J Melief
1Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
European Journal of Immunology
|February 1, 1992
Summary
Graft-vs-host reaction (GVHR) in F1 mice typically doesn't cause acute GVHD without donor stem cells. Donor stem cell repopulation prevents severe GVHD, even with major histocompatibility complex differences.
Area of Science:
- Immunology
- Transplantation Biology
Background:
- Graft-vs-host reaction (GVHR) in F1 mice usually lacks acute GVH disease (GVHD) unless major histocompatibility complex (MHC) differences exist.
- Acute GVHD signs stem from host lymphohemopoietic system destruction, leading to immunodeficiency, wasting, and death.
Purpose of the Study:
- Investigate if donor stem cell repopulation prevents clinical signs of acute GVHD in F1 mice.
- Determine the role of stem cells in the absence of GVHD in specific parent-F1 combinations.
Main Methods:
- Induced GVHR in (C57BL/10 x DBA/2J)F1 (BDF1) mice using DBA/2J lymph node (LN) cells (lacking stem cells).
- Administered DBA/2J spleen and LN cells (containing stem cells) to assess repopulation effects.
- Monitored for clinical signs of acute GVHD and detected alloreactive anti-host cytotoxic T lymphocyte (CTL) activity.
Main Results:
- GVHR induced with DBA/2J LN cells (no stem cells) led to acute GVHD in BDF1 mice.
- Clinical signs of GVHD (wasting, death) were prevented when donor stem cells repopulated the host lymphohemopoietic system.
- The protective effect of donor stem cells was more pronounced with different F1 strains.
Conclusions:
- Donor stem cell presence is critical in preventing acute GVHD in F1 mice, even with MHC disparities.
- Stem cell-mediated repopulation of the host immune system mitigates GVHD severity.
- Alloreactive CTLs likely contribute to host immune system destruction during acute GVHD.