SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen
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-signa...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004769/?tool=EBI |
| _version_ | 1818264961840840704 |
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| author | Anu Autio Huan Wang Francisco Velázquez Gail Newton Charles A. Parkos Pablo Engel Daniel Engelbertsen Andrew H. Lichtman Francis W. Luscinskas |
| author_facet | Anu Autio Huan Wang Francisco Velázquez Gail Newton Charles A. Parkos Pablo Engel Daniel Engelbertsen Andrew H. Lichtman Francis W. Luscinskas |
| author_sort | Anu Autio |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T19:43:14Z |
| format | Article |
| id | doaj.art-b3c42c1c18214cdab9a0768dbaa52277 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:43:14Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b3c42c1c18214cdab9a0768dbaa522772022-12-22T00:14:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01174SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleenAnu AutioHuan WangFrancisco VelázquezGail NewtonCharles A. ParkosPablo EngelDaniel EngelbertsenAndrew H. LichtmanFrancis W. LuscinskasThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004769/?tool=EBI |
| spellingShingle | Anu Autio Huan Wang Francisco Velázquez Gail Newton Charles A. Parkos Pablo Engel Daniel Engelbertsen Andrew H. Lichtman Francis W. Luscinskas SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen PLoS ONE |
| title | SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen |
| title_full | SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen |
| title_fullStr | SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen |
| title_full_unstemmed | SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen |
| title_short | SIRPα - CD47 axis regulates dendritic cell-T cell interactions and TCR activation during T cell priming in spleen |
| title_sort | sirpα cd47 axis regulates dendritic cell t cell interactions and tcr activation during t cell priming in spleen |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004769/?tool=EBI |
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