Abstract
ABSTRACTIt 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.
Highlights
Naïve T cells make fate decisions within hours after antigen exposure, resulting in activation, proliferation and either long-term memory or abortive effector responses, which correlate with T cell-DCs interaction kinetics [1– 4]
In this work we found that combined ICAM-1 and ICAM-2 deficiency on resident lymph node DCs stimulated with anti CD40 and immunized with soluble antigen did not impair their ability to arrest naïve CD4 lymphocytes entering these lymph nodes from blood and did not abrogate their subsequent in vivo differentiation into Th1 and Tfh effectors [13]
In order to assess the role of DC ICAMs in naïve T cell activation by migratory DCs [20] primed in the skin and entering popliteal lymph nodes, we generated in vitro BMDC, from the BM of either WT or ICAM1 and −2 double KO ( ICAM-1/2 DKO) mice and stimulated these antigen presenting cells with LPS 24 h prior to injection (Figure 1(a))
Summary
Naïve T cells make fate decisions within hours after antigen exposure, resulting in activation, proliferation and either long-term memory or abortive effector responses, which correlate with T cell-DCs interaction kinetics [1– 4]. In order to assess the role of DC ICAMs in naïve T cell activation by migratory DCs [20] primed in the skin and entering popliteal lymph nodes, we generated in vitro BMDC, from the BM of either WT or ICAM1 and −2 double KO ( ICAM-1/2 DKO) mice and stimulated these antigen presenting cells with LPS 24 h prior to injection (Figure 1(a)).
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