CONICET | Buscador de Institutos y Recursos Humanos

We have previously demonstrated that administration of CpG-ODN emulsified in IFA (CpG-ODN+IFA) to 3 (young) and 18 (aged) month-old mice induces an accumulation of CD11b+Gr1+ myeloid cells, with immunoregulatory function in the spleen. In this study, we intended to characterize CD11b+Gr1+ isolated from aged CpG-ODN+IFA-treated mice.Ten days after administration of CpG-ODN+IFA, CD11b+Gr1+ myeloid cells from aged mice expressed higher levels of the myeloid lineage differentiation and maturation markers CD31 and CD124 compared to cells from non-treated mice (p<0.05) To evaluate their immunosuppressive function, myeloid cells were isolated from aged CpG-ODN+IFA-treated mice and cultured with T cells from normal young mice stimulated with anti-CD3/CD28. We observed a reduced T cell proliferative response compared with T cells alone or cultured with myeloid cells from non-treated mice (p<0.05). Arginase activity was significantly elevated in protein lysates of CD11b+Gr1+ myeloid cells isolated from CpG-ODN+IFA aged mice compared to cells from non-treated mice (p<0.01). Arginase inhibitor (NOR-NOHA) restored T cell proliferative response (p<0.05). The increased arginase activity was accompanied by high levels of IL-6 and IL-4, which are cytokines considered as arginase inductors.After CpG-ODN+IFA administration, the expansion of CD11b+Gr1+ myeloid cells in aged mice remained up to 40 days after injection, a longer period of time than in young mice (p<0.05), returning to normal levels after 80 days (p<0.05). At day 40 we still observed increased arginase activity in the spleen of aged mice, compared with young mice (p<0.05). These results show that CD11b+Gr1+ myeloid cells with immunomodulatory function persist for longer time in aged mice than in young mice.

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