CONICET | Buscador de Institutos y Recursos Humanos

Previously we demonstratedthat immunocomplexes (IC) generated by injecting OVA in the footpad ofimmunized mice that have anti-OVA antibodies, induce the migration of OVA+ neutrophilto draining popliteal lymph nodes (D-poLNs). In the present study we evaluatethe influence of neutrophils activated by IC on CD4 T cell response in lymphnodes. C57BL/6 mice were immunized with OVA emulsified in Freund?s completeadjuvant and 15 days later boosted with OVA emulsified in Freund?s incompleteadjuvant. Ten days after last immunization they were injected with OVA-FITC inthe footpad and D-poLNs were obtained 6 to 48 h later; saline solution wasinjected on footpad corresponding to control non-draining popliteal lymph nodes(ND-poLNs). OVA+ neutrophils migrated to D-poLNs 6 h after OVAinjection (p<0.001) and at 12 h they were no longer detected. At longer times, we observed that total number ofD-poLNs cells increase (p<0.01). Particularly, a greater number of CD4 Tcells were detected at 48 h in D-poLNs compared to ND-poLNs (p<0.001). Naïve(p<0.05), effector memory (p<0.01) and central memory (p<0.001) subtypeswere increased. Interesting, CD4 T cells exhibited higher expression of CD69(p<0.001) and Ki67 (p<0.001) and higher production of IFNg (p<0.05)and IL17 (p<0.05) when compared to CD4 T cells in ND-poLNs. Moreover,D-poLNs showed an increase in Foxp3+CD25+ Treg population (p<0.001). In order to confirm theinfluence of neutrophils in CD4 T cells response, we treated mice withanti-Ly6G to deplete neutrophils. We observed a lower number of total poLNscells (p<0.001), CD4 T cells (p<0.01) and Treg cells (p<0.01) inD-poLNs from mice depleted of neutrophils compare to D-poLNs from isotypetreated mice. Besides, CD4 T cells and Tregs showed lower levels of Ki67(p<0.05) when mice were treated with anti-Ly6G. These findings indicate thatOVA+ neutrophilsin D-poLNs promote CD4 T cells proliferation and activation, as well as thedevelopment of Tregs.

enviar mensaje