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Essential Role of the Thymus to Reconstitute Naive (CD45RA+) T-Helper Cells After Human Allogeneic Bone Marrow Transplantation
Andreas Heitger,
Nikolaus Neu,
Hannelore Kern,
Eva-Renate Panzer-Grümayer,
Hildegard Greinix,
David Nachbaur,
Dietger Niederwieser, and
Franz Martin Fink
From the University Children's Hospital Innsbruck, Innsbruck, Austria; the Children's Cancer Research Institute, St Anna Children's Hospital Vienna, Vienna, Austria; the University Hospital Vienna, Department of Internal Medicine, Vienna, Austria; and the University Hospital Innsbruck, Department of Internal Medicine, Division of Clinical Immunobiology, Innsbruck, Austria.
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/µL at 6 months and 463 of 558/µL at 24 months after BMT, CD45RA+ of CD4+ cells), whereas CD45RA+ cells remained low (<60/µL). 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 ( 28% in adults and 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/µL at 6 months and 596 of 1,046/µL 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.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 850-857
© 1997 by The American Society of Hematology.
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