Format

Send to

Choose Destination
See comment in PubMed Commons below
Transplantation. 2005 Nov 15;80(9):1316-22.

Recipient-specific tolerance after HLA-mismatched umbilical cord blood stem cell transplantation.

Author information

  • 1Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-7284, USA.

Abstract

BACKGROUND:

Lower incidence and severity of acute graft versus host disease (GVHD) has been observed in leukemia patients receiving HLA-mismatched umbilical cord (UCB) transplants. However, despite the increased use of UCB in stem cell transplantation, the mechanisms underlying these favorable outcomes are not well delineated.

METHODS:

We analyzed antigen specific lymphocyte responses after transplant to determine whether the decreased allogeneic responsiveness of UCB lymphocytes is attributable to pan-unresponsiveness, lymphocyte repressive or recipient-specific tolerance.

RESULTS:

Circulating lymphocytes collected early (3 months) after UCB transplant demonstrate a less naïve phenotype compared with that in the infused graft. Additionally, after transplant, circulating peripheral blood UCB-derived lymphocytes produced normal levels of interferon-gamma and proliferated normally when stimulated with mitogen or third party alloantigen. In contrast, when stimulated with recipient antigen, circulating lymphocytes emerging posttransplant did not proliferate nor produce interferon-gamma. Moreover, analysis of interleukin-4 production revealed a Th2 response to recipient antigens. These data indicate early induction of immune tolerance of naïve UCB graft lymphocytes with skewing of transplant recipient-specific immune response towards Th2 cytokine profile.

CONCLUSIONS:

UCB graft lymphocyte immune naivety and observed early tolerance induction may contribute to the observed favorable GVHD incidence, despite infusion of HLA mismatch grafts in the unrelated allogeneic setting.

PMID:
16314801
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Lippincott Williams & Wilkins
    Loading ...
    Write to the Help Desk