Alterio de Goss, Mariagabriela;
Holtappels, Rafaela;
Steffens, Hans-Peter;
Podlech, Jürgen;
Angele, Peter;
Dreher, Liane;
Thomas, Doris;
Reddehase, Matthias J.
Control of Cytomegalovirus in Bone Marrow Transplantation Chimeras Lacking the Prevailing Antigen-Presenting Molecule in Recipient Tissues Rests Primarily on Recipient-Derived CD8 T Cells
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Medientyp:
E-Artikel
Titel:
Control of Cytomegalovirus in Bone Marrow Transplantation Chimeras Lacking the Prevailing Antigen-Presenting Molecule in Recipient Tissues Rests Primarily on Recipient-Derived CD8 T Cells
Beteiligte:
Alterio de Goss, Mariagabriela;
Holtappels, Rafaela;
Steffens, Hans-Peter;
Podlech, Jürgen;
Angele, Peter;
Dreher, Liane;
Thomas, Doris;
Reddehase, Matthias J.
Erschienen:
American Society for Microbiology, 1998
Erschienen in:
Journal of Virology, 72 (1998) 10, Seite 7733-7744
Sprache:
Englisch
DOI:
10.1128/jvi.72.10.7733-7744.1998
ISSN:
0022-538X;
1098-5514
Entstehung:
Anmerkungen:
Beschreibung:
ABSTRACTCytomegalovirus (CMV) infection during the transient immunodeficiency after bone marrow transplantation (BMT) develops into disease unless antiviral CD8 T cells are restored in due course. Histoincompatibility between donor and recipient is associated with increased risk. Complications may include a rejection response against the foreign major histocompatibility complex (MHC) antigens and a lack of antiviral control resulting from a misfit between donor-derived T cells and the antigenic viral peptides presented in recipient tissues. Here we have established a murine model of CMV disease after experimental BMT performed across a single MHC class I disparity. Specifically, BALB/c bone marrow cells expressing the prevailing antigen-presenting molecule Ldwere transplanted into the Ldgene deletion mutant BALB/c-H-2dm2, an experimental setting that entails a selective risk of host-versus-graft but not graft-versus-host response. The reconstituted T-cell population proved to be chimeric in that it consisted of Ld-positive donor-derived and Ld-negative recipient-derived cells. Pulmonary infiltrates did not include cytolytic T cells directed against Ld. This finding implies that the infection did not trigger a host-versus-graft response. Notably, upon adoptive transfer, donor-derived CD8 T cells preferentially protected tissues of donor genotype, whereas recipient-derived CD8 T cells protected tissues of either genotype. We infer from these data that the focus on immunodominant antigens presented by Ldwithin the donor cell population distracted the donor T cells from protecting recipient tissues and that protection in the chimeras was therefore primarily based on recipient T cells. As a consequence, T-cell chimerism after BMT should give a positive prognosis with respect to control of CMV.