In:
The Journal of Immunology, The American Association of Immunologists, Vol. 171, No. 11 ( 2003-12-01), p. 6023-6031
Abstract:
Infusion of donor antiviral T cells can provide protective immunity for recipients of hemopoietic progenitor cell transplants, but may cause graft-vs-host disease (GVHD). Current methods of separating antiviral T cells from the alloreactive T cells that produce GVHD are neither routine nor rapid. In a model of lethal murine CMV (MCMV) infection following MHC-mismatched bone marrow transplantation, infusion of MCMV-immune donor lymphocytes pretreated with the DNA cross-linking compound amotosalen prevented MCMV lethality without producing GVHD. Although 95% of mice receiving 30 × 106 pretreated donor lymphocytes survived beyond day +100 without MCMV disease or GVHD, all mice receiving equivalent numbers of untreated lymphocytes rapidly died of GVHD. In vitro, amotosalen blocked T cell proliferation without suppressing MCMV peptide-induced IFN-γ production by MCMV-primed CD8+ T cells. In vivo, pretreated lymphocytes reduced hepatic MCMV load by 4-log10 and promoted full hemopoietic chimerism. Amotosalen-treated, MCMV tetramer-positive memory (CD44high) CD8+ T cells persisted to day +100 following infusion, and expressed IFN-γ when presented with viral peptide. Pretreated T cells were effective at preventing MCMV lethality over a wide range of concentrations. Thus, amotosalen treatment rapidly eliminates the GVHD activity of polyclonal T cells, while preserving long-term antiviral and graft facilitation effects, and may be clinically useful for routine adoptive immunotherapy.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.171.11.6023
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2003
detail.hit.zdb_id:
1475085-5
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