CPG-ODN Induces, In Vivo And In Vitro, Myeloid Gr1+ Cd11b+ Cells And Supresor Functions In Young And Aged Mice.

FLORENCIA HARMAN; ROMINA P. RANOCCHIA; CAROLINA GORLINO; BELKYS A. MALETTO; GABRIEL MORÓN; MARÍA C PISTORESI- PALENCIA.

Buenos Aires

Congreso; First French-Argentine Immunology Congress y LVIII Reunión Anual de la Sociedad Argentina de Inmunología.; 2010

Sociedad Argentina de Inmunología.

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 CpG-ODN plus IFNg 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 IFNg 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.