Effects of preexisting autoimmunity on heart graft prolongation after donor-specific transfusion and anti-CD154

Transplantation. 2014 Jan 15;97(1):12-9. doi: 10.1097/TP.0b013e3182a77eba.


Background: Alloreactive memory T cells prevent costimulatory blockade-induced heart graft survival in mice, but whether and how preexisting autoreactive T cells affect solid-organ transplants under these conditions is unknown.

Methods: We tested the impact of preexisting cardiac myosin (CM)-specific immunity on murine heart transplant recipients treated with donor-specific transfusion (DST) plus anti-CD154 monoclonal antibody MR1.

Results: Preimmunization with CM but not control ovalbumin abrogated the graft prolonging effects of DST/MR1, whether administered 2 weeks or more than 6 weeks before transplantation. Adoptive transfer of spleen cells from CM-immunized mice into naïve recipients had similar effects. CM-specific immunity did not cross-react with donor antigens and preimmunization with CM had no impact on the survival or histology of DST/MR1-treated syngeneic heart grafts, the latter indicating that persistent autoimmunity is insufficient to cause rejection in the context of costimulatory blockade. We observed that the CM preimmunized mice produced higher frequencies of donor-reactive T cells with higher ratios of CD8/CD4Foxp3 cells, suggesting that the autoreactive memory T cells provide help for activation of alloreactive T cells despite the costimulatory blockade.

Conclusions: These mechanistic insights linking autoimmunity and alloimmunity in a model of murine heart transplantation have clinical relevance to the known association between autoimmunity and an elevated risk of acute and chronic heart transplant injury in humans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Autoantigens / administration & dosage
  • Autoantigens / immunology*
  • Autoimmunity / drug effects*
  • CD40 Ligand / immunology*
  • Cardiac Myosins / administration & dosage
  • Cardiac Myosins / immunology*
  • Cells, Cultured
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Heart Transplantation* / adverse effects
  • Immunization / methods*
  • Immunologic Memory / drug effects
  • Immunosuppressive Agents / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Models, Animal
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Time Factors


  • Antibodies, Monoclonal
  • Autoantigens
  • Immunosuppressive Agents
  • CD40 Ligand
  • Cardiac Myosins