Stable contacts of naïve CD4 T cells with migratory dendritic cells are ICAM-1-dependent but dispensable for proliferation in vivo

Abstract

It is unclear if naïve T cells require dendritic cell ICAMs to proliferate inside lymph nodes. To check if and when CD4 lymphocytes use ICAMs on migratory DCs, wild-type and ICAM-1 and 2 double knock out bone marrow-derived DCs pulsed with saturating levels of an OT-II transgene-specific ovalbumin-derived peptide were co-transferred into skin-draining lymph nodes. Intravital imaging of OT-II lymphocytes entering these lymph nodes revealed that ICAM-1 and −2 deficient migratory DCs formed fewer stable conjugates with OT-II lymphocytes but promoted normal T cell proliferation. DC ICAMs were also not required for unstable TCR-dependent lymphocyte arrests on antigen presenting migratory DCs. Thus, rare antigen-stimulated ICAM-stabilized T-DC conjugates are dispensable for CD4 lymphocyte proliferation inside lymph nodes.

Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 Differentially Contribute to Peripheral Activation and CNS Entry of Autoaggressive Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis

“…Furthermore, we found no role for T-cell expressed ICAM-1 and ICAM-2 in triggering MOG aa35−55 induced T-cell activation, suggesting a precise and non-interchangeable relationship in the molecular interactions between APCs and T cells at the IS. Our observations are in apparent contrast with previous studies failing to identify a role for ICAM-1 and ICAM-2 on DCs in inducing T-cell proliferation (58,59). Discrepancies between these studies might be due to subtle differences in experimental setups, including use of different DC polarization protocols and the use of different T-cell subsets, which may result in different TCR-pMHC affinity, ultimately affecting induction of T-cell proliferation.…”

Role of Extracellular Vesicles in Autoimmune Pathogenesis

“…Its pathogenesis primarily involves genetic, environmental, and immune components ( 42 ). MS is an inflammatory cascade triggered by autoreactive effector T cells and is associated with immune cells such as B cells, macrophages, and natural killer cells ( 43 – 46 ). It has been found that medullary EVs present in the cerebrospinal fluid are derived from microglia, and microglia will generate and release IL1-β and MHC-II, indicating that EVs secreted by reactive myeloid cells may trigger neuroinflammation and contribute to the rapid spread and presentation of antigens ( 47 ).…”

Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse

“…However, these results have to be interpreted with care due to the severe homing defects of these T cells. In contrast, deletion of ICAM1 on lymph node-resident (Feigelson et al, 2018) and migratory DCs (Kozlovski et al, 2019) appears to have no effect on initial T cell activation and proliferation but is crucial for the development of immunological memory . To address these points, we performed hock co-injections of differently labelled and peptide-loaded wt and hem1-/-DCs, followed by intravenously injected labelled OT-II T cells.…”

“…Deletion of LFA-1 or talin in T cells leads to strong in vivo T cell proliferation defects ( Kandula and Abraham, 2004 ; Wernimont et al, 2011 ); however, these results have to be interpreted with care due to the severe homing defects of these T cells. In contrast, deletion of ICAM1 on lymph node–resident ( Feigelson et al, 2018 ) and migratory DCs ( Kozlovski et al, 2019 ) appears to have no effect on initial T cell activation and proliferation, but is crucial for the development of immunological memory ( Scholer et al, 2008 ). To address these points, we performed hock co-injections of differently labeled and peptide-loaded WT and hem1 −/− DCs, which were followed by i.v.…”