동종 조혈모세포이식 후 급성 이식편대 숙주반응 시 T 세포의 OX-40 표현

Abstract

Background:Acute GRAFT-VERSUS-HOST disease (GVHD) is a major and often lethal consequence of allogeneic stem cell transplantation. The OX-40 molecule is a 50-kD glycoprotein that is expressed on recently activated CD4+ T cells. Although recently studies in rat model have suggested an close association between OX-40 expression on peripheral blood CD 4+ T cells and course of acute GVHD, there have been few studies in human yet. This study was performed to investigate whether the kinetics of repopulation of T cells in human recipients of HLA-matched allogeneic stem cell transplantation and their OX-40 expression would be predictive of acute GVHD and/or its response to immunosuppressive therapy. Methods:OX-40 expression on T cells was evaluated in 16 patients with hematologic malignancies or aplastic anemias, who received allogeneic stem cell transplantation between December 1998 and September 1999, at the Yonsei University College of Medicine, Severance Hospital. 10 donors were evaluated for control. Blood samples of the recipients were taken at day 14 before allogeneic stem cell transplantation and +10, +17, +24 after allogeneic stem cell transplantation. Blood samples of the donors were taken at day 2 before allogeneic stem cell transplantation. All staining was performed with monoclonal antibodies and OX-40, CD4, CD8 expression on lymphocytes was analyzed by flow cytometry. Mixed chimerism was determined by using the variable number of tandem repeats (VNTR) by polymerase chain reaction (PCR) in one patient. Results:OX-40 expression on CD4+ T lymphocytes of healthy donors and recipients before stem cell transplantation was with a mean percentage of 8.1±4.6%(1.7～16.9%), 15.5±7.8% (2.4～27.2%). OX-40 expression by CD8+ T lymphocytes of healthy donors and stem cell transplantation recipients was undetectable. The expression of OX-40 as a percentage of the CD4+ cells of recipients after stem cell transplantation was increased at day +10, day +17, day +24 compared with at day -14 (p=0.01, 0.02, 0.01, respectively). Six out of sixteen patients developed GVHD. OX-40 expression on CD4+ T lymphocytes of the patients with GVHD was 33.9±6.8%. But no difference in the kinetics of OX-40 expression by CD4+ T cells was observed between the patients that did or did not develop GVHD, nor did the clinical effect of any treatment given for GVHD correlate with alterations in OX-40 expression by CD4+ T cells. After stem cell transplantation, one patient showed mixed chimerism in peripheral blood cells by VNTR-PCR in one patient analyzed. Conclusion: Our observation do not support the view that OX-40 expression is predictive of GVHD or is a useful tool for monitoring response to GVHD. In addition, earlier suggestions to develop a therapeutic approach aimed at the elimination of CD 4+ OX-40+ lymphocytes are not supported by our findings.