, 2012). In summary, using PSM, GemStone™ allows for a unique visualization resulting in multiple phenotypic biomarker correlations without the limitations of bivariate dot plots or subjective gating. This results in the ability to examine the relative timing of phenotypic changes during CD8 T-cell differentiation.
Using three markers, CD45RA, CD28, and CCR7, we Cyclopamine manufacturer identified four major CD8+ T-cell subsets in PBMCs of healthy donors. CD57, CD62L, CD27, and CD127 are frequently used in the identification of T-cell memory subsets but in this study were identified as branching markers. The branching aspect is difficult to identify in traditional methods of data analysis and may account for inconsistencies in the definition of immunological memory. Branched markers such as CD57, CD62L, CD27, and CD127 should not be used as primary staging markers. However, these markers may be useful in identification of the heterogeneous phenotypes in T-cell memory populations. Thus, subjective
gating may be replaced as more objective and automated methods like PSM become more available. We thank Beth Hill Selleckchem MK2206 and Smita Ghanekar for reviewing the manuscript and Perry Haaland and Bob Zigon for their helpful comments on the manuscript. Competing Financial Interests C.B.B. is a named inventor on patent applications claiming the use of the technology described in this publication and is the owner of Verity Software House, a company which sells the software used in the work reported here. V.C.M and M.S.I. are paid employees of BD Biosciences, a company which developed the flow cytometers and reagents used in this work. “
“Currently, three innovator IFN-β
products have been developed and approved for treatment of OSBPL9 patients with relapsing-remitting multiple sclerosis (RRMS) in the EU/US. Avonex (Biogen-IDEC) and Rebif (Merck Serono), formulated differently, are manufactured using a rDNA-based Chinese hamster ovary (CHO) cell expression system and are generically classified as IFN-β-1a. Betaseron (or Betaferon; Bayer), a rDNA derived IFN-β produced in Escherichia coli, is classified as IFN-β-1b and has markedly lower specific activity than IFN-β-1a ( Runkel et al., 1998 and Karpusas et al., 1998). A potential consequence of treatment with recombinant IFN-β is the development of antibodies to the biotherapeutic (Ross et al., 2000, Goodin, 2005 and Sominanda et al., 2007). Such antibodies are usually IgG and can be either non-neutralizing or neutralizing (NAbs) (Pachner, 2003, Perini et al., 2004 and Gneiss et al., 2008). The former simply bind to IFN-β without apparently affecting its intrinsic activity while the NAbs bind IFN-β molecules in a way that prevents binding of IFN-β to the cell surface type I IFN-receptors, thus inhibiting biological activity of IFN-β and reducing its efficacy.