title: T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events.
abstract: It is generally believed that homeostatic responses regulate T-cell recovery after peripheral stem cell transplantation (PSCT). We studied in detail immune recovery in relation to T-cell depletion and clinical events in a group of adult patients who underwent PSCT because of hematologic malignancies. Initially, significantly increased proportions of dividing naive, memory, and effector CD4(+) and CD8(+) T cells were found that readily declined, despite still very low numbers of CD4(+) and CD8(+) T cells. After PSCT, increased T-cell division rates reflected immune activation because they were associated with episodes of infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision circles (TRECs) were measured to monitor thymic output of naive T cells. Mean TREC content normalized rapidly after PSCT, long before naive T-cell numbers had significantly recovered. This is compatible with the continuous thymic production of TREC(+) naive T cells and does not reflect homeostatic increases of thymic output. TREC content was decreased in patients with GVHD and infectious complications, which may be explained by the dilution of TRECs resulting from increased proliferation. Combining TREC and Ki67 analysis with repopulation kinetics led to the novel insight that recovery of TREC content and increased T-cell division during immune reconstitution after transplantation are related to clinical events rather than to homeostatic adaptation to T-cell depletion. (Blood. 2002;99:3449-3453)
authors.affiliation: Department of Clinical Viro-Immunology, CLB/Sanquin, Amsterdam, The Netherlands.
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Elmar S
authors.initials: ES
authors.lastname: de Pauw
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Dörte
authors.initials: D
authors.lastname: Hamann
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002455:Cell Division; D003141:Communicable Diseases / Q000276:immunology; D015321:Gene Rearrangement; D019672:Genes, T-Cell Receptor / Q000235:genetics*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007107:Immune System / Q000166:cytology; D008212:Lymphocyte Depletion; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous