Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance

Immunity
Justin S A PerryChyi-Song Hsieh

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.

Citations

Jan 29, 2020·Annual Review of Immunology·Peter A SavageChristine H Miller
Nov 27, 2018·International Immunology·Kenta KondoYousuke Takahama
Aug 25, 2018·Seminars in Immunopathology·Kristofor GlintonEdward B Thorp
Feb 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Courtney A Iberg, Daniel Hawiger
Nov 14, 2018·Nature Reviews. Immunology·Ludger KleinChyi-Song Hsieh
Feb 4, 2021·Seminars in Immunopathology·Rosa Bacchetta, Kenneth Weinberg
Feb 2, 2021·Frontiers in Immunology·Takeshi Nitta, Hiroshi Takayanagi
Mar 19, 2020·Cellular Immunology·Hrishikesh S KulkarniAndrew E Gelman
Feb 22, 2021·Journal of Autoimmunity·Mohsen Khosravi-MaharlooeiMegan Sykes
Apr 16, 2021·Nature Communications·Nicoletta CaronniFederica Benvenuti
Jan 23, 2021·Annual Review of Immunology·Mar Cabeza-CabrerizoCaetano Reis E Sousa
Apr 19, 2021·Trends in Molecular Medicine·Ana Rita SousaMariana B Oliveira
Jun 8, 2021·Immunological Reviews·Takeshi NittaHiroshi Takayanagi

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