Other markers and phenotypes are utilized to further classify these cell populations, as well as to discriminate them from other myeloid cells with sup pressor cell function, this kind of as tumor linked macrophages. As shown in Table 1, numerous investigators have at tempted to even more classify MDSCs about the basis of several strategies: their rela tive expressions of CD11b plus the Ly6 superfamily , which is recognized from the GR 1 antibody ; their total immaturity; and their suppressive activity. In terms of their immaturity, most investigators use expression within the adhesion molecule PECAM 1 , due to the fact this marker is current on progenitor and blast myeloid cells, together with poor expression of MHC II and costimulatory molecules CD80/86.
By way of example, we now have reported that just after sepsis, approximately 30% of the CD11b GR one splenocyte pop ulation expresses CD31, and lower than 3% with the population expresses MHC II. The suppressor action within MDSC populations has also been linked with a variety of markers which includes full report macrophage colony stimulating component receptor and inter leukin four receptor . To add to this heterogeneity, MDSC popula tions from a number of inflammatory states also have various

numbers of ma ture myeloid cells, this kind of as CD11c and F4/80 populations, dependant upon the experimental model. Within the CD11b GR 1 MDSC popu lation, there have already been several efforts by investigators to determine more hugely en riched MDSC subpopulations that pos sess the immunosuppressive phenotype.
While the results have normally been conflicting and remain controversial, sev eral investigators have subdivided murine MDSCs into norxacin two subpopulations, termed polymorphonuclear MDSCs and mononuclear MDSCs, for the basis of their relative expression of CD11b, Ly6G and Ly6C. MO MDSCs are usually classified as CD11b Gr 1intLy6G Ly6Chigh cells, plus they often express higher levels of F4/80, CD115 and CCR2 compared with PMN MDSCs. These MDSCs are potently immunosuppressive, blocking antigen certain CD8 T lymphocyte professional liferation as a result of an iNOS mediated mechanism. In contrast, the PMN MDSCs, classified as being CD11b GR 1highLy6Cl wLy6G , are also immunosup pressive, but their mechanism of action are believed for being even more dependent on arginase and interferon . Conversely, the CD11b GR 1intermed/dim population is comprised of typically the MO MDSCs with Ly6CbrightLy6G expres sion and potent immunosuppressive phenotypes.
A picture is often worth a thousand words, along with the heterogeneity of your murine MDSC population is ideal re vealed in cytospin preparations from GR 1 enriched splenocytes from healthy, septic, traumatized, tumor bearing and other inflamed mice. Enriched for GR 1 cells, these splenic MDSCs re flect the true heterogeneity of your popu lation, ranging from what seem to be practically mature PMNs to your traditional ringed MDSCs , towards the more monocyte ringed , to the even more imma ture appearing monocyte blast like cell population.