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

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

IMMUNOLOGY AND CELL BIOLOGY

NATURE PUBLISHING GROUP

Año: 2011 vol. 46 p. 462 - 467

0818-9641

The ability of synthetic oligodeoxynucleotides containing unmethylated cytosine guanine motifs (CpG-ODN) to induce both stimulatoryand counter-regulatory responses offers novel opportunities for using these molecules as immunomodulatory agents in differenttherapeutic strategies. Here, we investigated the potential of CpG-ODN to activate the arginase (ARG) enzyme in vivo and focused onthe consequences of this activation in T-cell proliferation. Challenging mice subcutaneously with CpG-ODN emulsified in incompleteFreund?s adjuvant (IFA) induced ARG and reduced T-cell proliferation associated with CD3f chain downregulation. Interestingly,impaired T-cell expansion correlated with elevated levels of CD11b+Gr1+ myeloid cells localized near T-cell areas in the spleen.In addition, purified CD11b+ cells obtained from the spleen of CpG-ODN+IFA-treated mice exhibited increased ARG activity andARG I expression along with an augmented [3H]-L-arginine uptake. CD11b+ myeloid cells significantly suppressed T-cell proliferationand CD3f chain expression induced by a polyclonal stimulus. Furthermore, these effects could be recovered by the addition ofexcess L-arginine or by treatment of CD11b+ cells with a specific ARG inhibitor. This study provides a novel evidence that CpGODN+IFA are able to induce splenic CD11b+ cells with ARG activity, with this population being responsible for the impaired T-cellproliferation observed after the treatment with CpG-ODN+IFA. These results underscore a key role of CpG-ODN on ARG activityin vivo and add support to the growing body of evidence in favor of a counter-regulatory role for CpG-ODN in an immune response.