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Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-06-2085.
Submitted June 25, 2003
Accepted July 24, 2003
CD25 expression on donor CD4+ or CD8+ T cells is associated with an increased risk of graft-versus-host disease following HLA-identical stem cell transplantation in humans
Marta Stanzani, Sergio L R Martins, Rima M Saliba, Lisa S St John, Susan Bryan, Daniel Couriel, John McMannis, Richard E Champlin, Jeffrey J Molldrem, and Krishna V Komanduri*
Transplant Immunology Section, Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
Institute of Hematology and Medical Oncology Seragnoli, University of Bologna, Bologna, Italy
Department of Hematology, Fleury-Diagnostic Medical Center, Sao Paolo, SP, Brazil
* Corresponding author; email: kkomandu{at}mdanderson.org.
Graft-versus-host disease (GVHD) occurs in an unpredictable fashion in 30-50% of matched-related stem cell transplants. The presence of increased frequencies of CD4+CD25+ regulatory T cells in donor grafts has been shown to ameliorate GVHD following allogeneic transplantation in murine models. To determine whether a similar relationship exists in humans, we quantitated the co-expression of CD25 on CD4+ and CD8+ T cells within 60 donor grafts infused into matched siblings and examined GVHD incidence in the respective recipients. Recipients who developed GVHD received donor grafts containing significantly higher frequencies of CD4+ T cells co-expressing CD25 relative to those who did not (median 9.26% vs. 2.22%, p=0.004). Frequencies of donor graft CD8+ T cells co-expressing CD25 were also higher (0.65% vs. 0.14%, p=0.002). Furthermore, transplant recipients who received grafts containing fewer CD4+CD25+ and CD8+CD25+ T cells were less likely to develop acute GVHD, despite the fact that these donor-recipient pairs were similar to others with respect to relevant clinical variables. These data suggest that co-expression of CD4 and CD25 may be insufficient to identify regulatory T cells in humans and that the presence of increased frequencies and numbers of CD25+ T cells in donor grafts is associated with GVHD in transplant recipients.
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