Requirement of residual thymus to restore normal T-cell subsets after human allogeneic bone marrow transplantation

Background. To determine the effect of residual thymic activity in reconstituting the T-cell system after T cell-depleting therapy, we monitored T-cell subsets of a unique thymectomized cancer patient in comparison to thymus-bearing patients after allogeneic bone marrow transplantation (BMT). Methods. T cells and T-cell subsets previously shown in murine studies to be regulated by the thymus were analyzed by FAGS from 6 to >48 months after BMT, The investigation of thymus-bearing patients included 32 examinations of 9 children and 14 adults. None of the investigated cases had severe graft-versus-host disease or severe infections when examined. Results. In the thymectomized host, T-cell regeneration occurred by donor cell expansion and was characterized by two prominent features: (i) a persistent failure to regenerate naive (CD45RA(+)) T-helper cells (14%, median), consistent with the recently developed concept of a thymus-dependency; and (ii) persistently elevated proportions of CD3(+)CD4(-)CD8(-) cells (double-negative cells, median 29%), which were identified in T cell receptor (TCR)gamma delta(+) (22%, median of CD3(+) cells, 88% double negatives) but also TCR alpha beta(+) T-cell populations (78%, median of CD3(+) cells, 17% double negatives). In thymus-bearing patients, 10 of 12 and 6 of 14 examinations of children and adults, respectively, performed later than 12 months after BMT showed the proportion of CD4(+)CD45RA(+) cells appropriate for age (>52% and >28% in children and adults, respectively). Elevated double-negative cells (>10%) were found in only three patients, but none had elevated double-negative cells with a TCR alpha beta(+) phenotype. Conclusion. Residual thymic activity might, in addition to its well-established role for regenerating naive T-helper (CD4(+)CD45RA(+)) cells, control the expansion of double-negative cells, A normal T-cell subset regeneration in a proportion of thymus-bearing adult hosts indicates the potential of an effective residual thymic activity even beyond childhood.