Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation

Anita Sapoznikov; Stav Kozlovski; Nehora Levi; Sara W. Feigelson; Ofer Regev; Natalia Davidzohn; Shifra Ben-Dor; Rebecca Haffner-Krausz; Ester Feldmesser; Noa Wigoda; Ekaterina Petrovich-Kopitman; Moshe Biton; Ronen Alon

doi:10.1016/j.celrep.2023.112864

Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation

Anita Sapoznikov, Stav Kozlovski, Nehora Levi, Sara W. Feigelson, Ofer Regev, Natalia Davidzohn, Shifra Ben-Dor, Rebecca Haffner-Krausz, Ester Feldmesser, Noa Wigoda, Ekaterina Petrovich-Kopitman, Moshe Biton^*, Ronen Alon^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Lymphocyte priming in lymph nodes (LNs) was postulated to depend on the formation of stable T cell receptor (TCR)-specific immune synapses (ISs) with antigen (Ag)-presenting dendritic cells (DCs). The high-affinity LFA-1 ligand ICAM-1 was implicated in different ISs studied in vitro. We dissect the in vivo roles of endogenous DC ICAM-1 in Ag-stimulated T cell proliferation and differentiation and find that under type 1 polarizing conditions in vaccinated or vaccinia virus-infected skin-draining LNs, Ag-presenting DCs engage in ICAM-1-dependent stable conjugates with a subset of Ag-specific CD8 blasts. Nevertheless, in the absence of these conjugates, CD8 lymphocyte proliferation and differentiation into functional cytotoxic T cells (CTLs) and skin homing effector lymphocytes takes place normally. Our results suggest that although CD8 T cell blasts engage in tight ICAM-1-dependent DC-T ISs, firm ISs are dispensable for TCR-triggered proliferation and differentiation into productive effector lymphocytes.

Original language	English
Article number	112864
Number of pages	23
Journal	Cell Reports
Volume	42
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2023.112864
Publication status	Published - 29 Aug 2023

Funding

Funding Information: We thank Prof. Steffen Jung for critical review of the manuscript. We also thank Prof. Wolfgang Kastenumuller (University of Würzburg) and Dr. Rony Dahan for providing reagents and Profs. Britta Engelhardt and Steffen Jung for the provision of mice. We thank Drs. Dena Leshkowitz, Gil Stelzer, and Ron Rotkopf for their assistance in the bioinformatic and statistical analysis and Dr. Hadas Keren-Shaul from the Sandbox Unit of the WIS Life Sciences Core Facilities for help with the scRNA-seq experiments. Funding was supplied by the Israel Science Foundation ( 791/17 to R.A., 1587 to M.B.), Minerva Stiftung (to R.A. and M.B.), the Moross Integrated Cancer Center (to R.A. and M.B.), the Helen and Martin Kimmel Institute for Stem Cell Research (to R.A. and M.B.), the Center for New Scientists at the Weizmann Institute of Science (to M.B.), the German Israeli Foundation ( I-1470-412.13/2018 to R.A.), the Israel Cancer Research Fund ( 19-109-PG to R.A.), the EU Horizon 2020 Research and Innovation Program (Ri-boMed 857119 to R.A.), Yeda-Sela Center for Basic Research (to R.A.), the Meyer Henri Cancer Endowment (to R.A.), William and Marika Glide and Carol A. Milett (to R.A.), the Linda Jacobs Chair in Immune and Stem Cell Research (to R.A.), and the Ernst and Kaethe Ascher Career Development Chair in Life Sciences (to M.B.).

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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Cite this

Sapoznikov, A., Kozlovski, S., Levi, N., Feigelson, S. W., Regev, O., Davidzohn, N., Ben-Dor, S., Haffner-Krausz, R., Feldmesser, E., Wigoda, N., Petrovich-Kopitman, E., Biton, M., & Alon, R. (2023). Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation. Cell Reports, 42(8), Article 112864. https://doi.org/10.1016/j.celrep.2023.112864

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title = "Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation",

abstract = "Lymphocyte priming in lymph nodes (LNs) was postulated to depend on the formation of stable T cell receptor (TCR)-specific immune synapses (ISs) with antigen (Ag)-presenting dendritic cells (DCs). The high-affinity LFA-1 ligand ICAM-1 was implicated in different ISs studied in vitro. We dissect the in vivo roles of endogenous DC ICAM-1 in Ag-stimulated T cell proliferation and differentiation and find that under type 1 polarizing conditions in vaccinated or vaccinia virus-infected skin-draining LNs, Ag-presenting DCs engage in ICAM-1-dependent stable conjugates with a subset of Ag-specific CD8 blasts. Nevertheless, in the absence of these conjugates, CD8 lymphocyte proliferation and differentiation into functional cytotoxic T cells (CTLs) and skin homing effector lymphocytes takes place normally. Our results suggest that although CD8 T cell blasts engage in tight ICAM-1-dependent DC-T ISs, firm ISs are dispensable for TCR-triggered proliferation and differentiation into productive effector lymphocytes.",

author = "Anita Sapoznikov and Stav Kozlovski and Nehora Levi and Feigelson, {Sara W.} and Ofer Regev and Natalia Davidzohn and Shifra Ben-Dor and Rebecca Haffner-Krausz and Ester Feldmesser and Noa Wigoda and Ekaterina Petrovich-Kopitman and Moshe Biton and Ronen Alon",

year = "2023",

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doi = "10.1016/j.celrep.2023.112864",

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Sapoznikov, A, Kozlovski, S , Levi, N , Feigelson, SW, Regev, O, Davidzohn, N, Ben-Dor, S , Haffner-Krausz, R , Feldmesser, E , Wigoda, N , Petrovich-Kopitman, E , Biton, M & Alon, R 2023, 'Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation', Cell Reports, vol. 42, no. 8, 112864. https://doi.org/10.1016/j.celrep.2023.112864

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T1 - Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation

AU - Sapoznikov, Anita

AU - Kozlovski, Stav

AU - Levi, Nehora

AU - Feigelson, Sara W.

AU - Regev, Ofer

AU - Davidzohn, Natalia

AU - Ben-Dor, Shifra

AU - Haffner-Krausz, Rebecca

AU - Feldmesser, Ester

AU - Wigoda, Noa

AU - Petrovich-Kopitman, Ekaterina

AU - Biton, Moshe

AU - Alon, Ronen

PY - 2023/8/29

Y1 - 2023/8/29

N2 - Lymphocyte priming in lymph nodes (LNs) was postulated to depend on the formation of stable T cell receptor (TCR)-specific immune synapses (ISs) with antigen (Ag)-presenting dendritic cells (DCs). The high-affinity LFA-1 ligand ICAM-1 was implicated in different ISs studied in vitro. We dissect the in vivo roles of endogenous DC ICAM-1 in Ag-stimulated T cell proliferation and differentiation and find that under type 1 polarizing conditions in vaccinated or vaccinia virus-infected skin-draining LNs, Ag-presenting DCs engage in ICAM-1-dependent stable conjugates with a subset of Ag-specific CD8 blasts. Nevertheless, in the absence of these conjugates, CD8 lymphocyte proliferation and differentiation into functional cytotoxic T cells (CTLs) and skin homing effector lymphocytes takes place normally. Our results suggest that although CD8 T cell blasts engage in tight ICAM-1-dependent DC-T ISs, firm ISs are dispensable for TCR-triggered proliferation and differentiation into productive effector lymphocytes.

AB - Lymphocyte priming in lymph nodes (LNs) was postulated to depend on the formation of stable T cell receptor (TCR)-specific immune synapses (ISs) with antigen (Ag)-presenting dendritic cells (DCs). The high-affinity LFA-1 ligand ICAM-1 was implicated in different ISs studied in vitro. We dissect the in vivo roles of endogenous DC ICAM-1 in Ag-stimulated T cell proliferation and differentiation and find that under type 1 polarizing conditions in vaccinated or vaccinia virus-infected skin-draining LNs, Ag-presenting DCs engage in ICAM-1-dependent stable conjugates with a subset of Ag-specific CD8 blasts. Nevertheless, in the absence of these conjugates, CD8 lymphocyte proliferation and differentiation into functional cytotoxic T cells (CTLs) and skin homing effector lymphocytes takes place normally. Our results suggest that although CD8 T cell blasts engage in tight ICAM-1-dependent DC-T ISs, firm ISs are dispensable for TCR-triggered proliferation and differentiation into productive effector lymphocytes.

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Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation

Abstract

Funding

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