Allochimeric molecules and mechanisms in abrogation of cardiac allograft rejection

T. Spencer Skelton, Neelam Tejpal, Yongquan Gong, Jacek Z. Kubiak, Malgorzata Kloc, R. Mark Ghobrial

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Dendritic cells are professional antigen presenting cells that perform antigen processing and antigen presentation functions and rely on the proper functioning and distribution of the endoplasmic reticulum (ER) and Golgi apparatus and of vesicular trafficking pathways. We previously developed a model system to study the mechanisms governing inhibition of chronic rejection of heart allografts. Heterotopic cardiac transplants were placed intra-abdominally and the major histocompatibility class (MHC) class I allochimeric molecule, [α1h1/u]-RT1.Aa, which contains donor-type (Wistar Furth, WF; RT1u) immunogenic epitopes displayed on recipient-type (ACI, RT1a) sequences, was delivered by portal vein to the recipients of heterotopic hearts. Dendritic cells were isolated from the recipient bone marrow at 1 and 3 days after transplantation and were immunostained or processed for Western blotting with anti-RhoB, translationally controlled tumor protein (TCTP), Sprouty-related (Spred1) protein, ER, and Golgi antibodies. Western blotting analyses showed the downregulation of RhoB GTPase, TCTP, and Spred1 in dendritic cells isolated from allochimeric molecule-treated rats. Immunostaining showed that in these cells, Spred 1 was shifted to the base of cellular processes, Rho B formed nonvesicular band in the cell equator, and TCTP was highly enriched in the cell nucleus. The Golgi apparatus was drastically reduced in size and formed a tiny nonvesicular aggregate, and the ER partially lost vesicular appearance. The function of allochimeric molecule in the abrogation of heart allograft rejection may rely on the downregulation of RhoB pathway components that regulate the structure and function of the ER/Golgi/vesicular trafficking pathways involved in antigen processing and presentation by dendritic cells.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalJournal of Heart and Lung Transplantation
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • antigen presentation
  • dendritic cell
  • ER
  • Golgi
  • RhoB
  • Spred1
  • TCTP

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

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