Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation

Kenneth Weinberg, Bruce R. Blazar, John E. Wagner, Edward Agura, Brenna J. Hill, Monika Smogorzewska, Richard A. Koup, Michael R. Betts, Robert H. Collins, Daniel C. Douek

Research output: Contribution to journalArticle

338 Citations (Scopus)

Abstract

Hematopoietic stem cell transplantation (HSCT) is followed by profound immunodeficiency. Thymic function is necessary for de novo generation of T cells after HSCT. Circulating CD45RA+ naive T-cell levels are predictive of antigen-specific T-cell responses in the absence of graft-versus-host disease (GVHD). These T cells may not represent recent thymic emigrants, since naive T cells may maintain this phenotype if not antigen-activated. To accurately measure thymic output after HSCT and determine the factors that influence thymic function, T-cell receptor excision circles (TRECs) were examined. In CD4+ and CD8+ cells from a cross-section of patients following HSCT. TREC levels rose weeks after HSCT and could be detected in patients 6 years after HSCT. TREC levels correlated with the frequency of phenotypically naive T cells, indicating that such cells were not expanded progeny of naive T cells present in the donor graft. Chronic GVHD was the most important factor that predicted low TREC levels even years after HSCT. Patients with a history of resolved GVHD had decreased numbers of TREC, compared with those with no GVHD. Because few adults had no history of GVHD, it was not possible to determine whether age alone inversely correlated with TREC levels. Recipients of cord blood grafts had no evidence of decreased TREC induced by immunosuppressive prophylaxis drugs. Compared with unrelated donor grafts, recipients of matched sibling grafts had higher TREC levels. Collectively, these data suggest that thymopoiesis is inhibited by GVHD. Larger studies will be needed to determine the independent contributions of age and preparative regimen to post-transplant thymopoietic capacity.

Original languageEnglish (US)
Pages (from-to)1458-1466
Number of pages9
JournalBlood
Volume97
Issue number5
DOIs
StatePublished - Mar 1 2001

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Hematopoietic Stem Cell Transplantation
T-Cell Antigen Receptor
Stem cells
Grafts
T-cells
Graft vs Host Disease
T-Lymphocytes
Transplants
Antigens
Unrelated Donors
Immunosuppressive Agents
Fetal Blood
Siblings
Tissue Donors
Phenotype
Blood
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology

Cite this

Weinberg, K., Blazar, B. R., Wagner, J. E., Agura, E., Hill, B. J., Smogorzewska, M., ... Douek, D. C. (2001). Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood, 97(5), 1458-1466. https://doi.org/10.1182/blood.V97.5.1458

Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. / Weinberg, Kenneth; Blazar, Bruce R.; Wagner, John E.; Agura, Edward; Hill, Brenna J.; Smogorzewska, Monika; Koup, Richard A.; Betts, Michael R.; Collins, Robert H.; Douek, Daniel C.

In: Blood, Vol. 97, No. 5, 01.03.2001, p. 1458-1466.

Research output: Contribution to journalArticle

Weinberg, K, Blazar, BR, Wagner, JE, Agura, E, Hill, BJ, Smogorzewska, M, Koup, RA, Betts, MR, Collins, RH & Douek, DC 2001, 'Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation', Blood, vol. 97, no. 5, pp. 1458-1466. https://doi.org/10.1182/blood.V97.5.1458
Weinberg K, Blazar BR, Wagner JE, Agura E, Hill BJ, Smogorzewska M et al. Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood. 2001 Mar 1;97(5):1458-1466. https://doi.org/10.1182/blood.V97.5.1458
Weinberg, Kenneth ; Blazar, Bruce R. ; Wagner, John E. ; Agura, Edward ; Hill, Brenna J. ; Smogorzewska, Monika ; Koup, Richard A. ; Betts, Michael R. ; Collins, Robert H. ; Douek, Daniel C. / Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. In: Blood. 2001 ; Vol. 97, No. 5. pp. 1458-1466.
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