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

R. RANOCCHIA, C. GORLINO, M.I. CRESPO, F. HARMAN, M. LISCOVSKY, G. MORÓN, B. MALETTO, M. C. PISTORESI-PALENCIA

NATURE PUBLISHING GROUP

Año: 2011

he 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 subcutaneously with CpG-ODN emulsified in incomplete Freund?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 and ARG I expression along with an augmented [3H]-L-arginine uptake. CD11b+ myeloid cells signi