Anti-IL15 Monoclonal antibody, clone EOU26Sb [APC]

Background: Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce. Methods: We studied gene expression of a broad panel of cytokines in WB from relapsing-remitting multiple sclerosis (RRMS) patients in remission and healthy controls (HCs). Subsequently we determined the gene expression of the dysregulated cytokines in isolated PBMC subsets (CD4(+), CD8(+)T-cells, NK-cells, B-cells, monocytes and dendritic cells) from RRMS patients and HCs and in CSF-cells from RRMS patients in clinical relapse and noninflammatory neurological controls (NIND). Results: RRMS patients had increased expression of IFN-gamma (IFNG), interleukin (IL) 1-beta (IL1B), IL7, IL10, IL12A, IL15, IL23, IL27, lymphotoxin-alpha (LTA) and lymphotoxin-beta (LTB) in WB. In PBMC subsets the main sources of pro-inflammatory cytokines were T- and B-cells, whereas monocytes were the most prominent source of immunoregulatory cytokines. In CSF-cells, RRMS patients had increased expression of IFNG and CD19 and decreased expression of IL10 and CD14 compared to NINDs. CD19 expression correlated with expression of IFNG, IL7, IL12A, IL15 and LTA whereas CD14 expression correlated with IL10 expression. Conclusions: Using a systematic approach, we show that expression of pro-inflammatory cytokines in peripheral blood primarily originates from T- and B-cells, with an important exception of IFNG which is most strongly expressed by NK-cells. In CSF-cell studies, B-cells appear to be enriched in RRMS and associated with expression of pro-inflammatory cytokines; contrarily, monocytes are relatively scarce in CSF from RRMS patients and are associated with IL10 expression. Thus, our findings suggest a pathogenetic role of B-cells and an immunoregulatory role of monocytes in RRMS.

In mammals, successful pregnancy is dependent in part on the adaptation or regulation of the maternal immune system to prevent the rejection of the embryonic semiallograft. A modification in Th cell function and secretion is a requirement for the establishment and maintenance of pregnancy. Although there is strong evidence from studies in humans and mice linking successful pregnancy with the predominance of Th2-type immunity, the situation in cattle remains unclear. This study describes the characterization of the immune response of the bovine maternal endometrium to the presence of a developing embryo, with specific emphasis on the macrophage and dendritic cell populations and associated factors, using quantitative real-time PCR, in situ hybridization, and immunohistochemistry. Furthermore, in vivo and in vitro models were developed to investigate the potential role of progesterone and interferon-tau (IFNT) in the regulation of these immune factors. There was a marked increase in the population of CD14(+) cells and CD172a-CD11c(+) cells in the endometrium in response to pregnancy, which was paralleled by increased mRNA expression of a number of non-Th-associated factors, including IL12B and IL15, and downregulation of IL18. In addition, we identified several novel IFNT- and progesterone-regulated factors, including IL12B, MCP1, MCP2, PTX3, RSAD2, and TNFA, whose regulation may be critical to pregnancy outcome. Our findings give center stage to non-Th cells, such as monocytes/macrophages and dendritic cells, in the bovine immune response to the semiallogenic embryo. In conclusion, we propose that in cattle, successful pregnancy establishment is associated with a dramatic regulation of the cytokine network, primarily by endometrial monocytes/macrophages and dendritic cells.