Arginase-dependent suppression by CpG-ODN plus IFA-induced splenic myeloid CD11b+Gr1+ cells

RANOCCHIA, R; GORLINO, C; CRESPO, MI; HARMAN, MF; LISCOVSKY, M; MORóN, G; MALETTO, B; PISTORESI, MC

IMMUNOLOGY AND CELL BIOLOGY

NATURE PUBLISHING GROUP

Año: 2011 p. 1 - 12

0818-9641

The ability of synthetic oligodeoxynucleotides containing unmethylated cytosine guanine motifs (CpG-ODN) to induce both stimulatory and counter-regulatory responses offers novel opportunities for using these molecules as immunomodulatory agents in different therapeutic strategies. Here, we investigated the potential of CpG-ODN to activate the arginase (ARG) enzyme in vivo and focused on the consequences of this activation in T cell proliferation. Challenging mice via s.c. with CpG-ODN emulsified in incomplete Freund´s adjuvant (IFA) induced ARG and reduced T cell proliferation associated with CD3ζ chain down-regulation. Interestingly, impaired T cell expansion correlated with elevated levels of CD11b+Gr1+ myeloid cells localized near T-cell areas in spleen. In addition, purified CD11b+ cells obtained from the spleen of CpG-ODN+IFA-treated mice exhibited increased ARG activity and ARG I expression along with an augmented [3H]-L-arginine uptake. CD11b+ myeloid cells significantly suppressed T cell proliferation and CD3ζ chain expression induced by a polyclonal stimulus. Furthermore, these effects could be recovered by the addition of excess L-arginine or by treatment of CD11b+ cells with a specific ARG inhibitor. This study provides a novel evidence that CpG-ODN+IFA are able to induce splenic CD11b+ cells with ARG activity, with this population being responsible for the impaired T-cell proliferation observed after the treatment with CpG-ODN+IFA. These results underscore a key role of CpG-ODN on ARG activity in vivo and add support to the growing body of evidence in favor of a counter-regulatory role for CpG-ODN in an immune response.