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

作者：Ranocchia Romina P; Gorlino Carolina V; Crespo Maria I; Harman Maria F; Liscovsky Miriam V; Moron Gabriel; Maletto Belkys A; Pistoresi Palencia Maria C^*

来源：Immunology and Cell Biology, 2012, 90(7): 710-721.

DOI：10.1038/icb.2011.98

• CpG-ODN
• IFA
• immunosuppression
• myeloid cells
• T cell

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 subcutaneously with CpG-ODN emulsified in incomplete Freund's adjuvant (IFA) induced ARG and reduced T-cell proliferation associated with CD3 zeta 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 [H-3]-L-arginine uptake. CD11b(+) myeloid cells significantly suppressed T-cell proliferation and CD3 zeta 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. Immunology and Cell Biology (2012) 90, 710-721; doi:10.1038/icb.2011.98; published online 15 November 2011

• 出版日期2012-8