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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4344-4352.
Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-07-2534.

Submitted July 25, 2003
Accepted February 6, 2004
Hematopoietic Stem Cell Dose Correlates with the Speed of Immune Reconstitution after Stem Cell Transplantation
Benny J Chen*, Xiuyu Cui, Gregory D Sempowski, Jos Domen, and Nelson J Chao
Bone Marrow Transplantation Program, Duke University Medical Center, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA
Department of Medicine, Duke University Medical Center, Durham, NC, USA; Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA
Bone Marrow Transplantation Program, Duke University Medical Center, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA; Department of Immunology, Duke University Medical Centeer, Durham, NC, USA
* Corresponding author; email: chen0032{at}mc.duke.edu.
In the current study, we tested whether higher numbers of hematopoietic stem cells correlate with the speed of immune reconstitution in a congenic transplantation model (C57BL/6, CD45.1, Thy1.1 C57BL/6, CD45.2, Thy1.2+) using purified hematopoietic stem cells (c-Kit+Thy1.1lowLin-/lowSca-1+). Three different doses of stem cells (400, 1000, 5000) were used. Phenotypic analyses in peripheral blood and spleen demonstrated that more stem cells infused are associated with more rapid regeneration of T cells (CD4+, CD8+, naive CD4+, naive CD8+) and B cells up to 10 weeks after transplantation. The numbers of T and B cells became equivalent among different dose groups at week +14. Production of interleukin-2 and interferon per T cell was similar regardless of stem cell dose even when tested at the time when there were significant differences in peripheral T cell counts. The improved immune recovery was attributed to a more rapid regeneration of donor-type immune cells. Higher numbers of total thymocytes and signal joint T cell receptor excision circles were observed in the higher dose stem cell recipients, suggesting accelerated regeneration of T cells was due to enhanced thymopoiesis.

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