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.
| Original language | English |
|---|---|
| Pages (from-to) | 849-859 |
| Number of pages | 11 |
| Journal | Cell Reports |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 23 Jan 2018 |
Funding
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.
All Science Journal Classification (ASJC) codes
- General Biochemistry,Genetics and Molecular Biology