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

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): 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
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.

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Teaser

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.