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Measurement of recipient-specific alloreactivity: is GVHD predictable?
M Theobald1, D Bunjes, T Nierle
1Department of Immunology, Scripps Research Institute, La Jolla, CA.
Bone Marrow Transplantation
|January 1, 1993
Summary
High frequencies of host-specific interleukin-2 (IL-2) secreting donor T lymphocyte precursors (Tl-p) before bone marrow transplantation (BMT) predict severe acute graft-versus-host disease (GVHD). Post-BMT detection of these cells also correlates with acute GVHD.
Area of Science:
- Immunology
- Transplantation Medicine
Background:
- Acute graft-versus-host disease (GVHD) is a major complication following allogeneic bone marrow transplantation (BMT).
- Predicting the severity of GVHD before BMT in HLA-identical sibling pairs remains challenging.
- A pre-transplant test to assess allogeneic reactivity is lacking.
Purpose of the Study:
- To determine the frequency of host-specific IL-2 secreting donor T lymphocyte precursors (Tl-p) before BMT.
- To correlate these precursor frequencies with the development of acute GVHD.
- To investigate the role of host-reactive Tl-p in GVHD induction and maintenance.
Main Methods:
- Quantified host-specific IL-2-secreting Tl-p in HLA-identical sibling pairs before BMT.
- Analyzed Tl-p phenotype, in vivo priming, and minor histocompatibility antigen recognition.
- Assessed host-specific Tl-p frequency post-BMT in patients with and without GVHD.
Main Results:
- High frequencies of host-specific Tl-p pre-BMT were detected in donors whose siblings developed severe (grade II/III) acute GVHD.
- Low frequencies were observed in donors whose siblings had mild (grade 0/I) GVHD.
- Post-BMT detection of host-specific Tl-p significantly correlated with severe acute GVHD.
Conclusions:
- Host-specific IL-2-secreting T cells are critically involved in acute GVHD induction.
- These T cells play a role in the maintenance of acute GVHD.
- Measuring host-specific Tl-p frequency may aid in predicting and managing GVHD post-BMT.