Th1/Th2 directed immune response in relation to the CCR5D32 genetic variant in human. Animal studies consistently show a more pronounced Th2 immune response Abmole Ifenprodil during genetic deficiency of CCR5 or pharmacological CCR5 blockade in atherosclerotic and other inflammatory conditions. In diet induced atherosclerotic inflammation in mice, genetic deletion of CCR5 was associated with a more stable plaque phenotype and reduced Th1 type immune response of stimulated splenocytes and an increased Th2 type response in splenocytes and lymph node cells. After wire injury in mice with CCR5 deficiency a more atheroprotective immune response was seen, i.e. low IFN-c and elevated IL-10 in CD4+ splenocytes compaired to CCR5 wild type mice. Also in genetically CCR5 deficient mice with diet induced atherosclerosis, reduced lesion size, increased IL-10 and decreased TNF-a production by CD4+ and CD8+ T cells, and reduced macrophage accumulation in plaques and lowered circulating IL-6 levels was seen. In CCR5 deficient mice a more CD4+ Th2 cell activation pattern was seen in colitis in contrast to CCR5 wild type mice. Interestingly, in CCR5 genetically deficient mice who received a renal allograft less Th1 associated markers and increased Th2 associated markers were found during chronic intragraft immune response. In an islet transplantation model it was shown that in genetically CCR5 deficient mice not only in the intragraft immune response but also in the periphery a Th2 shift occurred. In mice with dietinduced atherosclerosis treatment with a RANTES chemokine antagonist, hereby blocking CCR5, reduced atherosclerotic plaque formation, associated with reduced proliferation and secretion of Th1 cytokines IFN-c and TNF-a, without difference in Th2 cytokine profile. In rats pharmacological CCR5 blockade in stimulated endothelial cells inhibited selective transmigration of CD4+ Th1 cells. Our results extend these animal data on functional differences in immune response for the first time to a human setting and support our previous human cross-sectional Abmole ICG-001 association study, showing absence of association between serum CRP and TNF-a levels in ESRD patients carrying the CCR5D32 genotype, in contrast to patients without this genetic variant, supporting a reduced Th1 immune response in CCR5D32. It should be emphasized that ELISA and flowcytometry methods give different types of results and that measuring the intracellular cytokine production by FACS is more accurate than ELISA. The measured cytokines by ELISA can be released from several cells, whereas FACS-method identifies the intracellular cytokines produced on a single-cell level.