RECONSTITUTION OF CELLULAR-IMMUNITY AGAINST CYTOMEGALOVIRUS IN RECIPIENTS OF ALLOGENEIC BONE-MARROW BY TRANSFER OF T-CELL CLONES FROM THE DONOR

Background. Cytomegalovirus (CMV) disease in immunocompromised patient s correlates with a deficiency of CD8+ cytotoxic T lymphocytes specifi c for CMV. We evaluated the safety and immunologic effects of immunoth erapy with clones of these lymphocytes in recipients of allogeneic bon e marrow transplants. Methods. Clones of CD8+ cytotoxic T cells specif ic for CMV proteins were isolated from the blood of bone marrow donors . Fourteen patients each received four intravenous infusions of these clones from their donors beginning 30 to 40 days after marrow transpla ntation. The reconstitution of cellular immunity against CMV was monit ored before and during the period of infusions and for up to 12 weeks after the final infusion. The rearranged genes encoding the T-cell rec eptor served as markers in evaluating the persistence of the transferr ed T cells. Results. No toxic effects related to the infusions were ob served. Cytotoxic T cells specific for CMV were reconstituted in all p atients. In vitro measurements showed that cytotoxic activity against CMV was significantly increased (P<0.001) after the infusions in 11 pa tients who were deficient in such activity before therapy. The level o f activity achieved after the infusions was similar to that measured i n the donors. Analysis of rearranged T-cell-receptor genes in T cells obtained from two recipients indicated that the transferred clones per sisted for at least 12 weeks. Cytotoxic-T-cell activity declined in pa tients deficient in CD4+ T-helper cells specific for CMV, suggesting t hat helper-T-cell function is needed for the persistence of transferre d CD8+ T cells. Neither CMV viremia nor CMV disease developed in any o f the 14 patients. Conclusions. The transfer of CMV-specific clones of CD8+ T cells derived from the bone marrow donor is a safe and effecti ve way to reconstitute cellular immunity against CMV after allogeneic marrow transplantation.