6533b7d4fe1ef96bd1263207
RESEARCH PRODUCT
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
Jürgen PodlechMariagabriela Alterio De GossHans-peter SteffensPeter AngeleLiane DreherDoris ThomasRafaela HoltappelsMatthias J. Reddehasesubject
Lung DiseasesAdoptive cell transferImmunologyAntigen-Presenting CellsViral Pathogenesis and ImmunityCD8-Positive T-LymphocytesMajor histocompatibility complexMicrobiologyMajor Histocompatibility ComplexChimera (genetics)MiceAntigenVirologyMHC class ImedicineCytotoxic T cellAnimalsAntigen-presenting cellMice Inbred BALB CBone TransplantationbiologyChimeraVirologymedicine.anatomical_structureInsect ScienceImmunologyCytomegalovirus Infectionsbiology.proteinBone marrowdescription
ABSTRACT Cytomegalovirus (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 L d were transplanted into the L d gene deletion mutant BALB/c-H-2 dm2 , 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 L d -positive donor-derived and L d -negative recipient-derived cells. Pulmonary infiltrates did not include cytolytic T cells directed against L d . 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 L d within 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1998-10-01 |