Infectious tolerance to ADP/ATP carrier peptides induced by anti-L3T4 monoclonal antibody in dilated cardiomyopathy mice

J Clin Immunol. 2005 Jul;25(4):376-84. doi: 10.1007/s10875-005-4187-y.

Abstract

CD4 T cells are suspected to play an important role in the pathogenesis of dilated cardiomyopathy (DCM). This study sought to evaluate whether anti-L3T4 monoclonal antibody (McAb) could induce the infectious tolerance to the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier peptides to protect mice from DCM. BALB/c mice (n = 16) were immunized with the peptides derived from human ADP/ATP carrier on the 1st, 14th, 28th, 49th, and 79th days, and some of them (n = 6) were also injected with anti-L3T4 McAb on the -1st, 0, and 1st days. On the 180th day, the splenocytes (SC) from the McAb-treated group were transferred into the syngeneic recipients (n = 6) who were also immunized with the peptides in the same manner. The sham-immunized mice were taken as the controls (n = 10). Results showed that the serum antibody against the ADP/ATP carrier examined with ELISA was positive in all mice only immunized with the peptides (DCM group), while negative in the McAb-treated, the SC-transferred, and the Control groups. The mRNA expression of IFN-gamma, IL-2, and IL-4, especially IL-4 in T cells investigated using real-time quantitative PCR and the percentages of T helper 1 (Th1) and Th2 subsets, especially Th2 subset detected with Flow Cytometry were all increased in DCM group, accompanied by the cardiac histopathological changes like those in DCM. Such findings were not seen in the other three groups. It concluded that anti-L3T4 McAb could inhibit the occurrence of DCM induced by the ADP/ATP carrier peptides in mice, and this immune tolerance could be transferred to the syngeneic recipients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • CD4 Antigens / immunology*
  • Cardiomyopathy, Dilated / enzymology*
  • Cardiomyopathy, Dilated / immunology*
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / prevention & control
  • Cytokines / genetics
  • Cytokines / metabolism
  • Humans
  • Immune Tolerance / immunology*
  • Lymphocyte Transfusion
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitochondrial ADP, ATP Translocases / immunology*
  • Peptides / administration & dosage*
  • Peptides / chemical synthesis
  • Peptides / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / transplantation
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Th1 Cells / enzymology
  • Th1 Cells / immunology
  • Th1 Cells / transplantation
  • Th2 Cells / enzymology
  • Th2 Cells / immunology
  • Th2 Cells / transplantation

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • Cytokines
  • Peptides
  • Mitochondrial ADP, ATP Translocases