SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen

PLoS One. 2022 Apr 12;17(4):e0266566. doi: 10.1371/journal.pone.0266566. eCollection 2022.

Abstract

The SIRPα-CD47 axis plays an important role in T cell recruitment to sites of immune reaction and inflammation but its role in T cell antigen priming is incompletely understood. Employing OTII TCR transgenic mice bred to Cd47-/- (Cd47KO) or SKI mice, a knock-in transgenic animal expressing non-signaling cytoplasmic-truncated SIRPα, we investigated how the SIRPα-CD47 axis contributes to antigen priming. Here we show that adoptive transfer of Cd47KO or SKI Ova-specific CD4+ T cells (OTII) into Cd47KO and SKI recipients, followed by Ova immunization, elicited reduced T cell division and proliferation indices, increased apoptosis, and reduced expansion compared to transfer into WT mice. We confirmed prior reports that splenic T cell zone, CD4+ conventional dendritic cells (cDCs) and CD4+ T cell numbers were reduced in Cd47KO and SKI mice. We report that in vitro derived DCs from Cd47KO and SKI mice exhibited impaired migration in vivo and exhibited reduced CD11c+ DC proximity to OTII T cells in T cell zones after Ag immunization, which correlates with reduced TCR activation in transferred OTII T cells. These findings suggest that reduced numbers of CD4+ cDCs and their impaired migration contributes to reduced T cell-DC proximity in splenic T cell zone and reduced T cell TCR activation, cell division and proliferation, and indirectly increased T cell apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens
  • CD47 Antigen* / genetics
  • CD47 Antigen* / metabolism
  • Cell Communication
  • Dendritic Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic* / genetics
  • Receptors, Immunologic* / metabolism
  • Spleen* / immunology
  • Spleen* / metabolism
  • T-Lymphocytes / metabolism

Substances

  • Antigens
  • CD47 Antigen
  • Ptpns1 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic