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

Cytomegalovirus (CMV) infection during the transient immunodeficiency after bone marrow transplantation (BMT) develops into disease unless a ntiviral CD8 T cells are restored in due course. Histoincompatibility between donor and recipient is associated with increased risk. Complic ations may include a rejection response against the foreign major hist ocompatibility complex (MHC) antigens and a lack of antiviral control resulting from a misfit between donor-derived T cells and the antigeni c viral peptides presented in recipient tissues. Here we have establis hed a murine model of CMV disease after experimental BMT performed acr oss a single MHC class I disparity. Specifically, BALB/c bone marrow c ells expressing the prevailing antigen-presenting molecule L-d were tr ansplanted into the Ld gene deletion mutant BALB/c-H-2(dm2), an experi mental setting that entails a selective risk of host-versus-graft but not graft-versus-host response. The reconstituted T-cell population pr oved 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 t hat the infection did not trigger a host-versus-graft response. Notabl y, upon adoptive transfer, donor-derived CD8 T cells preferentially pr otected tissues of donor genotype, whereas recipient-derived CD8 T cel ls protected tissues of either genotype. We infer from these data that the focus on immunodominant antigens presented by L-d within the dono r cell population distracted the donor T cells from protecting recipie nt 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.