CD36 Mediates Cell-Surface Antigens to Promote Thymic Development of the Regulatory T Cell Receptor Repertoire and Allo-tolerance

Justin S.A. Perry, Emilie V. Russler-Germain, You W. Zhou, Whitney Purtha, Matthew L. Cooper, Jaebok Choi, Mark A. Schroeder, Vanessa Salazar, Takeshi Egawa, Byeong Chel Lee, Nada A. Abumrad, Brian S. Kim, Mark S. Anderson, John F. DiPersio, Chyi Song Hsieh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α+ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α+ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens. The absence of CD8α+ DCs or CD36 altered thymic T cell selection, as evidenced by TCR repertoire analysis and the loss of allo-tolerance in murine allogeneic BM transplantation (allo-BMT) studies. Decreases in these DCs and CD36 expression in peripheral blood of human allo-BMT patients correlated with graft-versus-host disease. Our findings suggest that CD36 facilitates transfer of mTEC-derived cell-surface antigen on CD8α+ DCs to promote tolerance to host antigens during homeostasis and allo-BMT. How cooperative antigen presentation between medullary thymic epithelial cells (mTECs) and dendritic cells (DCs) occurs remains unknown. Perry et al. show that CD36, a scavenger receptor expressed on CD8α+ DCs, mediates acquisition and presentation of cell-surface antigens from mTECs for T cell receptor repertoire development and allo-tolerance during bone marrow transplantation.

Original languageEnglish
Pages (from-to)923-936.e4
JournalImmunity
Volume48
Issue number5
DOIs
StatePublished - May 15 2018

Keywords

  • CD36
  • antigen transfer
  • apoptotic cell clearance
  • efferocytosis
  • medullary thymic epithelial cells
  • regulatory T cells
  • scavenger receptor
  • thymic dendritic cells
  • tolerance

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