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

Abstract

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)

• Authors: E P Hochberg, A C Chillemi, C J Wu, D Neuberg, C Canning, K Hartman, E P Alyea, R J Soiffer, S A Kalams, J Ritz
• Journal: Blood (Blood) Vol. 98 Issue 4 Pg. 1116-21 (Aug 15 2001) ISSN: 0006-4971 [Print] United States
• PMID: 11493459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

• Adult
• Bone Marrow Transplantation (methods)
• Case-Control Studies
• Cell Differentiation (immunology, physiology)
• Female
• Gene Rearrangement, T-Lymphocyte (physiology)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (therapy)
• Leukopoiesis (immunology)
• Lymphocyte Depletion
• Male
• Middle Aged
• T-Lymphocytes (physiology)
• Time Factors
• Transplantation Conditioning
• Transplantation, Homologous (methods)