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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1116-1121
IMMUNOBIOLOGY
Quantitation of T-cell neogenesis in vivo after allogeneic bone
marrow transplantation in adults
Ephraim P. Hochberg,
Antoinette C. Chillemi,
Catherine J. Wu,
Donna Neuberg,
Christine Canning,
Kelly Hartman,
Edwin P. Alyea,
Robert J. Soiffer,
Spyros A. Kalams, and
Jerome Ritz
From the Disease Center for Hematologic Oncology,
Department of Adult Oncology, Department of Biostatistics, Dana-Farber
Cancer Institute; Department of Medicine, Brigham and Women's
Hospital; Partners AIDS Research Center, Massachusetts General
Hospital; and Harvard Medical School, Boston MA.
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.
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