| First Author | Ryzhov S | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 11 | Pages | 6120-9 |
| PubMed ID | 22039302 | Mgi Jnum | J:179751 |
| Mgi Id | MGI:5303012 | Doi | 10.4049/jimmunol.1101225 |
| Citation | Ryzhov S, et al. (2011) Adenosinergic regulation of the expansion and immunosuppressive activity of CD11b+Gr1+ cells. J Immunol 187(11):6120-9 |
| abstractText | Extracellular adenosine and purine nucleotides are elevated in many pathological situations associated with the expansion of CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs). Therefore, we tested whether adenosinergic pathways play a role in MDSC expansion and functions. We found that A(2B) adenosine receptors on hematopoietic cells play an important role in accumulation of intratumoral CD11b(+)Gr1(high) cells in a mouse Lewis lung carcinoma model in vivo and demonstrated that these receptors promote preferential expansion of the granulocytic CD11b(+)Gr1(high) subset of MDSCs in vitro. Flow cytometry analysis of MDSCs generated from mouse hematopoietic progenitor cells revealed that the CD11b(+)Gr-1(high) subset had the highest levels of CD73 (ecto-5'-nucleotidase) expression (Deltamean fluorescence intensity [MFI] of 118.5 +/- 16.8), followed by CD11b(+)Gr-1(int) (DeltaMFI of 57.9 +/- 6.8) and CD11b(+)Gr-1(-/low) (DeltaMFI of 12.4 +/- 1.0) subsets. Even lower levels of CD73 expression were found on Lewis lung carcinoma tumor cells (DeltaMFI of 3.2 +/- 0.2). The high levels of CD73 expression in granulocytic CD11b(+)Gr-1(high) cells correlated with high levels of ecto-5'-nucleotidase enzymatic activity. We further demonstrated that the ability of granulocytic MDSCs to suppress CD3/CD28-induced T cell proliferation was significantly facilitated in the presence of the ecto-5'-nucleotidase substrate 5'-AMP. We propose that generation of adenosine by CD73 expressed at high levels on granulocytic MDSCs may promote their expansion and facilitate their immunosuppressive activity. |
