Essential role of the thymus to reconstitute naive (CD45RA(+)) T-helper cells after human allogeneic bone marrow transplantation

To contribute to the understanding of the role of the thymus in humans in the reconstitution of naive (CD45RA(+)) T cells after bone marrow transplantation (BMT), we compared T-cell regeneration in a unique situation, namely a thymectomized cancer patient (15 years old), with that of thymus-bearing patients after allogeneic BMT. These cases shared features of transplantation (total body irradiation, HLA-matched donors, and graft-versus-host disease prophylaxis with cyclosporine A) and all had an uncomplicated posttransplantation course. As shown by fluorescence-activated cell sorting analyses, the thymectomized host failed to reconstitute CD45RA(+) T-helper cells even 24 months after BMT (11% CD45RA(+) of CD4(+) cells). In this patient, preferentially CD45RO(+) cells contributed to the recovery of CD4(+) cells (206 of 261/mu L at 6 months and 463 of 558/mu L at 24 months after BMT, CD45RA(+) of CD4(+) cells), whereas CD45RA(+) cells remained low (<60/mu L). In contrast, nine thymus-bearing hosts (5 children and 4 adults) examined between 6 and 24 months after BMT effectively reconstituted CD4(+)/CD45RA(+) cells according to their normal age-related range (greater than or equal to 28% in adults and greater than or equal to 50% in children), Five of these were analyzed sequentially at 6 and 9 months after BMT. Within this period, CD45RA(+) cells increasingly contributed to the recovery of CD4(+) cells (median, +21%), even when total CD4(+) cells decreased, With respect to T-cytotoxic/suppressor cells, the thymectomized host retained the capacity to recover CD45RA(+) cells (137 of 333/mu L at 6 months and 596 of 1,046/mu L at 24 months after BMT, CD45RA(+) of CD8(+) cells), a proportion similar to that seen in thymus-bearing hosts, These findings suggest that a thymus-independent pathway exists to regenerate CD45RA(+) T-cytotoxic/suppressor cells, but residual thymus is essential to reconstitute naive (CD45RA(+)) T-helper cells after BMT in humans. (C) 1997 by The American Society of Hematology.