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

Autio, Anu ; Wang, Huan ; Velazquez, Francisco ; Newton, Gail ; Parkos, Charles A. ; Engel, Pablo ; Engelbertsen, Daniel LU ; Lichtman, Andrew H. and Luscinskas, Francis W. (2022) In PLoS ONE 17(4 April).
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,... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
T cells, Spleen, Flow cytometry, Cell staining, Computer software, Mouse models, Apoptosis, Cell cycle and cell division
in
PLoS ONE
volume
17
issue
4 April
article number
e0266566
pages
21 pages
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:85128155441
  • pmid:35413056
ISSN
1932-6203
DOI
10.1371/journal.pone.0266566
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 Autio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
a6aad50c-10d2-4cfc-af02-38418efd08a8
date added to LUP
2022-04-29 10:45:18
date last changed
2022-06-22 05:06:59
@article{a6aad50c-10d2-4cfc-af02-38418efd08a8,
  abstract     = {{<p>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. </p>}},
  author       = {{Autio, Anu and Wang, Huan and Velazquez, Francisco and Newton, Gail and Parkos, Charles A. and Engel, Pablo and Engelbertsen, Daniel and Lichtman, Andrew H. and Luscinskas, Francis W.}},
  issn         = {{1932-6203}},
  keywords     = {{T cells; Spleen; Flow cytometry; Cell staining; Computer software; Mouse models; Apoptosis; Cell cycle and cell division}},
  language     = {{eng}},
  number       = {{4 April}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0266566}},
  doi          = {{10.1371/journal.pone.0266566}},
  volume       = {{17}},
  year         = {{2022}},
}