2078 LYMPHOPENIA-INDUCED PROLIFERATION OF LYMPHOCYTES RESULTS IN CHRONIC REJECTION OF MICE CARDIAC ALLOGRAFTS

Abstract

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery I1 Apr 20102078 LYMPHOPENIA-INDUCED PROLIFERATION OF LYMPHOCYTES RESULTS IN CHRONIC REJECTION OF MICE CARDIAC ALLOGRAFTS Shoichi Iida, Kazuya Omoto, Daisuke Tokita, Hideki Ishida, Kazunnari Tanabe, and Ryo Abe Shoichi IidaShoichi Iida Tokyo, Japan More articles by this author , Kazuya OmotoKazuya Omoto Tokyo, Japan More articles by this author , Daisuke TokitaDaisuke Tokita Tokyo, Japan More articles by this author , Hideki IshidaHideki Ishida Tokyo, Japan More articles by this author , Kazunnari TanabeKazunnari Tanabe Tokyo, Japan More articles by this author , and Ryo AbeRyo Abe Chiba, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2138AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lymphopenia-induced proliferation (LIP) is a normal physiological process that maintains a constant level of T cells in lymphopenic conditions. As naïve T cells undergo LIP in the absence of overt antigenic stimulation, they progressively acquire the phenotypic and functional characteristics of antigen-specific memory T cells. Transplantation is a rare example in which lymphopenia is deliberately induced for its immunosuppressive effect, and the continuous administration of immunosuppressive drugs frequently induces lymphopenia in the recipient. Our objective was to assess the influence of LIP of lymphocytes on allograft function and rejection after achieving donor-specific transplant tolerance by costimulatory blockade. METHODS Vascularized heterotopic, cervical heart transplantation from donors (BALB/C) to recipient (C57BL/6) was performed. Donor-specific transplant tolerance was induced by high-dose costimulation blockade (C.B.). To produce lymphopenic conditions, some recipient mice were irradiated with a sublethal dose of 6.5 Gy on days 60–70 after transplantation. At various time points after subtotal lymphocyte depletion, alloreactivity was measured using a mixed lymphocyte reaction (MLR) assay. The population of T cells and intragraft infiltration of cells after LIP was analyzed by fluorescence-activated cell sorting (FACS) and other immunohistologically methods. RESULTS The high-dose C.B. regimen and cervical method allowed MHC-disparate heart graft transplantation almost permanently (average 376.1 days, median survival time (MST) 411 days). By contrast, after subtotal lymphodepletion, the allografts were rejected gradually (average 73.1 days, MST after irradiation 62.0 days). The MLR assay revealed that LIP eliminated the donor-specific tolerance, but this alloreactivity was lower than in untreated-rejection mice. FACS analysis showed that effector/memory T cells predominated markedly after subtotal lymphodepletion. Although the proportion of regulatory cells (CD4+Foxp3+) also increased after LIP, allograft rejection was accelerated. CONCLUSIONS These findings suggest that the resistance to donor-specific tolerance seen after subtotal lymphocyte depletion can be attributed to changes in the balance of naïve, memory, and regulatory T cells. These data have clinically relevant implications for transplantation protocols that use partial or complete peripheral T-cell depletion. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e808 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shoichi Iida Tokyo, Japan More articles by this author Kazuya Omoto Tokyo, Japan More articles by this author Daisuke Tokita Tokyo, Japan More articles by this author Hideki Ishida Tokyo, Japan More articles by this author Kazunnari Tanabe Tokyo, Japan More articles by this author Ryo Abe Chiba, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...