Título:
CpG-ODN INDUCES, IN VITRO AND IN VIVO, MYELOID GR1+CD11b+ CELLS AND SUPPRESSOR FUNCTIONS IN YOUNG AND AGED MICE
Autor/es:
HARMAN, MARÍA FLORENCIA; RANOCCHIA, ROMINA; GORLINO, CAROLINA; MALETTO, BELKYS; MORÓN, GABRIEL; PISTORESI, M CRISTINA
Resumen:
Besides the ability of CpG-ODN to induce in aged (18 months:18m) and young (3 months:3m) BALB/c mice a
powerful Th1 immune response, we showed that in vitro CpG-ODN is able to stimulate both, arginase and inducible nitric
oxide synthase (iNOS) in macrophages. In the present study, we investigate the regulatory ability of CpG-ODN in vitro and in
vivo in 3m and 18m mice and focused on the role of L-arginine metabolism.
Bone marrow (BM) cells from 3m and 18m mice were incubated with GM-CSF (3?4 days), resulting in similar
percentage of GR1+CD11b+ myeloid cells (3m:50±4%, 18m:55±5%). The treatment of BM-derived myeloid cells with CpGODN
plus IFN-γ induces arginase activity and nitric oxide (NO) production in both mice ages (p<0.05). When myeloid cells
from 18m mice were added to young normal mice splenocytes stimulated with Con A, we observed lower suppression of
proliferative response than their younger counterparts.
In addition, splenic T cells from CpG-ODN injected 3m and 18m mice shown reduced proliferation in response to
Con A compared with T cells from non-injected control mice (p<0.01). Thus, CpG-ODN induces an increase in Gr1+CD11b+
cell population (3m control:3,0±0,2% vs CpG:8,2±1,0%; 18m control 3,7±0,1% vs CpG:9,7±1,8%)(p<0.001) and high
arginase activity (p<0.05) in the spleen of injected mice compared to their not injected counterparts, but NO production
(p<0.05) only in 18m mice. Analysis of cytokines shows secretion of IFN-γ at both mice age, but IL-10 was significantly
higher after treatment with CpG-ODN only in young mice.
In conclusion, CpG-ODN is able to induce, in vitro and in vivo, myeloid Gr1+CD11b+ cells and T cell regulatory
functions in young and aged mice, likely employing the L-arginine metabolism. The ability of CpG-ODN to induce both
stimulatory and regulatory responses offers novel opportunities for the improvement of vaccines applied to elderly