@article{604393faa25748a996bde9e660fd57d2,
title = "ICAMs Are Not Obligatory for Functional Immune Synapses between Naive CD4 T Cells and Lymph Node DCs",
abstract = "Protective immune responses depend on the formation of immune synapses between T cells and antigen-presenting cells (APCs). The two main LFA-1 ligands, ICAM-1 and ICAM-2, are co-expressed on many cell types, including APCs and blood vessels. Although these molecules were suggested to be key players in immune synapses studied in vitro, their contribution to helper T cell priming in vivo is unclear. Here, we used transgenic mice and intravital imaging to examine the role of dendritic cell (DC) ICAM-1 and ICAM-2 in naive CD4 T cell priming and differentiation in skin-draining lymph nodes. Surprisingly, ICAM deficiency on endogenous CD40-stimulated lymph node DCs did not impair their ability to arrest and prime CD4 lymphocyte activation and differentiation into Th1 and Tfh effectors. Thus, functional T cell receptor (TCR)-specific helper T cell synapses with antigen-presenting DCs and subsequent proliferation and early differentiation into T effectors do not require LFA-1-mediated T cell adhesiveness to DC ICAMs.",
author = "Feigelson, \{Sara W.\} and Adam Solomon and Adi Biram and Miki Hatzav and Moria Lichtenstein and Ofer Regev and Stav Kozlovski and Diana Varol and Caterina Curato and Dena Leshkowitz and Steffen Jung and Ziv Shulman and Ronen Alon",
note = "We thank Dr. Britta Engelhardt (Bern) for providing ICAM-1 and ICAM-2 double deficient mice and Dr. Shelly Schwarzbaum for editorial assistance. We thank Dr. Michel Nussenzweig for the αDEC-205-OVA conjugate. We also thank Yoni Feigelson for coding assistance for cell motion analysis. The RNAseq work was performed under the guidance of Dr. Hadas Keren-Shaul from the Sandbox unit of the Life Science Core Facility of Weizmann Institute of Science. Z.S. is supported by the European Research Council (ERC) grant no. 677713 , the Morris Kahn Institute for Human Immunology, Human Frontiers of Science Program (CDA- 00023/2016 ), Azrieli Foundation and Rising Tide Foundation . R.A. is an incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research, and his research is supported by the Israel Science Foundation (grant 791/17 ), the Flight Attendant Medical Research Institute Foundation (grant 032001\_CoE ), the Minerva Foundation , Germany (grant 712020 ), and by a research grant from Mr. and Mrs. William Glied . Author contributions - S.W.F. designed, performed, and analyzed all experiments and prepared the manuscript; A.S. performed and analyzed some experiments; A.B. performed the imaging for Figure 3C and assisted with in vivo work; M.H., M.L., O.R., S.K., and D.V. assisted with the preparation of chimeras and in vivo experiments; C.C. assisted with the MARS-seq of Figures 4G and S4; D.L. performed the bioinformatic analysis for the MARS-seq shown in Figures 4G and S4; S.J. supervised the MARS-seq experiments; Z.S. performed the intravital microscopy experiments in Figure 5, designed and supervised experiments, and prepared the manuscript; R.A. designed and supervised all experiments and prepared the manuscript.",
year = "2018",
month = jan,
day = "23",
doi = "10.1016/j.celrep.2017.12.103",
language = "الإنجليزيّة",
volume = "22",
pages = "849--859",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier BV",
number = "4",
}