Quantitation of T-cell neogenesis in vivo after allogeneic bone marrow transplantation in adults

Following myeloablative therapy, it is unknown to what extent age-dependent thymic involution limits the generation of new T cells with a diverse repertoire. Normal T-cell receptor gene rearrangement in T-cell progenitors results in the generation of T-cell receptor rearrangement excision circles (T...

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Veröffentlicht in:Blood 2001-08, Vol.98 (4), p.1116-1121
Hauptverfasser: Hochberg, Ephraim P., Chillemi, Antoinette C., Wu, Catherine J., Neuberg, Donna, Canning, Christine, Hartman, Kelly, Alyea, Edwin P., Soiffer, Robert J., Kalams, Spyros A., Ritz, Jerome
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Sprache:eng
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Zusammenfassung:Following myeloablative therapy, it is unknown to what extent age-dependent thymic involution limits the generation of new T cells with a diverse repertoire. Normal T-cell receptor gene rearrangement in T-cell progenitors results in the generation of T-cell receptor rearrangement excision circles (TRECs). In this study, a quantitative assay for TRECs was used to measure T-cell neogenesis in adult patients with leukemia who received myeloablative therapy followed by transplantation of allogeneic hematopoietic stem cells. Although phenotypically mature T cells had recovered by 1 to 2 months after bone marrow transplantation (BMT), TREC levels remained low for 3 months after BMT. T-cell neogenesis became evident by 6 months, and normal levels of adult thymic function were restored at 6 to 12 months after BMT. Subsequent leukemia relapse in some patients was associated with reduced TREC levels, but infusion of mature donor CD4+ T cells resulted in rapid restoration of thymic function. These studies demonstrate that T-cell neogenesis contributes to immune reconstitution in adult patients and suggest that thymic function can be manipulated in vivo.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V98.4.1116