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 (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. (Blood. 2001;98:1116-1121)
Hochberg
E P
EP
Disease Center for Hematologic Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston MA 02115, USA.
Chillemi
A C
AC
Wu
C J
CJ
Neuberg
D
D
Canning
C
C
Hartman
K
K
Alyea
E P
EP
Soiffer
R J
RJ
Kalams
S A
SA
Ritz
J
J
D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D019891:Leukopoiesis / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000379:methods