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. 2010 Jul 15;90(1):4-13.
doi: 10.1097/TP.0b013e3181dfa694.

Autoimmunity to vimentin potentiates graft vasculopathy in murine cardiac allografts

Balakrishnan Mahesh  1 , Hon-Sing Leong, K Sukumaran Nair, Ann McCormack, Padmini Sarathchandra, Marlene L Rose
Affiliations

Autoimmunity to vimentin potentiates graft vasculopathy in murine cardiac allografts

Balakrishnan Mahesh et al. Transplantation. .

Abstract

Background: There is increasing evidence for a role for autoimmunity in transplant rejection. It has previously been shown that autoantibodies to vimentin (Vim) accelerate acute rejection of murine cardiac allografts. We have investigated whether autoimmunity to Vim contributes to development of cardiac allograft vasculopathy (CAV).

Methods: Two well-established minor mismatch murine models of CAV were used, transplantation of 129/sv hearts into T-cell-depleted C57Bl/6 (B6) recipients and transplantation of FVB hearts into nonimmunosuppressed DBA/1 recipients. Recipients were immunized with recombinant mouse Vim in complete Freunds adjuvant, and controls received hen egg lysozyme 2 weeks before transplantation. T cell and antibody responses to Vim were assessed by ELISPOT and ELISA, respectively. CAV within transplanted hearts was assessed by quantitative morphometry of occluded vessels, presence of smooth muscle cells, deposition of C3d, and confocal microscopy.

Results: Allografts were harvested from B6 recipients at days 30 and 45 and from DBA/1 recipients at days 18 and 35. At all days, there was significantly more intimal occlusion of arteries of Vim -immunized mice than controls. There was significantly more smooth muscle cell alpha actin in vessels from Vim-immunized mice, and more C3d deposited in hearts from Vim-immunized mice. Confocal microscopy demonstrated colocalization of Vim with C3d on endothelial cells, leukocytes, and platelets in allogeneic but not syngeneic hearts. Serum from Vim-immunized mice, but not controls, caused platelet/leukocyte conjugation when added to mouse leukocytes.

Conclusion: The autoimmune response to Vim accelerates CAV progression in these minor-mismatched models.

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