NEUTROPHILS ACTIVATED BY IMMUNOCOMPLEXES MODULATE CD4 T CELL RESPONSE IN LYMPH NODES

CASTELL,S; HARMAN, MF; MORÓN, G; MALETTO, B; PISTORESI, MC

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

Sociedades de Biociencia

Previously we demonstrated that immunocomplexes (IC) generatedby injecting OVA in the footpad of immunized mice that haveanti-OVA antibodies, induce the migration of OVA+ neutrophil todraining popliteal lymph nodes (D-poLNs). In the present study weevaluate the influence of neutrophils activated by IC on CD4 T cellresponse in lymph nodes.C57BL/6 mice were immunized with OVA emulsified in Freund?scomplete adjuvant and 15 days later boosted with OVA emulsified in Freund?s incomplete adjuvant. Ten days after last immunization theywere injected with OVA-FITC in the footpad and D-poLNs were obtained6 to 48 h later; saline solution was injected on footpad correspondingto control non-draining popliteal lymph nodes (ND-poLNs).OVA+ neutrophils migrated to D-poLNs 6 h after OVA injection(p<0.001) and at 12 h they were no longer detected. At longertimes, we observed that total number of D-poLNs cells increase(p<0.01). Particularly, a greater number of CD4 T cells were detectedat 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)subtypes were increased. Interesting, CD4 T cells exhibited higherexpression of CD69 (p<0.001) and Ki67 (p<0.001) and higher productionof IFNg (p<0.05) and IL17 (p<0.05) when compared to CD4T cells in ND-poLNs. Moreover, D-poLNs showed an increase inFoxp3+CD25+ Treg population (p<0.001).In order to confirm the influence of neutrophils in CD4 T cells response,we treated mice with anti-Ly6G to deplete neutrophils. Weobserved a lower number of total poLNs cells (p<0.001), CD4 T cells(p<0.01) and Treg cells (p<0.01) in D-poLNs from mice depletedof neutrophils compare to D-poLNs from isotype treated 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 that OVA+ neutrophils in D-poLNs promoteCD4 T cells proliferation and activation, as well as the developmentof Tregs.