The Experts below are selected from a list of 30600 Experts worldwide ranked by ideXlab platform
Jay A Levy - One of the best experts on this subject based on the ideXlab platform.
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the unexpected pleiotropic activities of RANTES
Journal of Immunology, 2009Co-Authors: Jay A LevyAbstract:The field of chemokines represented by the β-chemokine RANTES began just 20 years ago ([1][1]). Several of these small basic proteins were discovered about the same time and defined the process of chemotaxis, which today is an important component of our understanding of immune responses to
Ali H Hajeer - One of the best experts on this subject based on the ideXlab platform.
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chemokine RANTES promoter polymorphism affects risk of both hiv infection and disease progression in the multicenter aids cohort study
AIDS, 2000Co-Authors: David H Mcdermott, Matthew J Beecroft, Cynthia A Kleeberger, Fadwa M Alsharif, William E R Ollier, Peter A Zimmerman, Boakye A Boatin, Susan F Leitman, Roger Detels, Ali H HajeerAbstract:OBJECTIVE: To examine whether polymorphism in the RANTES gene is associated with HIV disease outcome. DESIGN: RANTES, a ligand of the major HIV co-receptor, CCR5, is known to block HIV-CCR5 interactions. Recently, two single nucleotide polymorphisms in the RANTES gene promoter region, designated -403G/A and -28C/G, have been described. Both polymorphisms can affect in-vitro promoter activity, and the RANTES -403A, -28G haplotype has been associated with a slower CD4 cell count decline rate in a Japanese cohort. METHODS: We compared RANTES compound genotype frequencies between HIV-positive and exposed-uninfected participants of the Multicenter AIDS Cohort Study (MACS) and rates of progression to AIDS for MACS seroconverters. RESULTS: We found that the two most common RANTES promoter compound genotypes, G1 (-403G/G, -28C/C) found in 67% of Caucasians, and G4 (-403G/A, -28C/C) found in 23% of Caucasians, were associated with altered risk of HIV transmission and progression, particularly in individuals who lacked the protective CCR5 mutation, CCR5delta32. In this study, individuals with a G4 compound genotype were more likely to acquire HIV than individuals with a G1 compound genotype (OR 1.72, P = 0.016) and the risk increased when individuals possessing CCR5delta32 were omitted from consideration (OR 2.13, P = 0.005). Among seroconverters lacking CCR5delta32, those who had the G4 compound genotype progressed significantly slower to AIDS-1993 than those with the G1 compound genotype (median time to AIDS 7.6 versus 5.4 years; RH 0.65; P = 0.007). CONCLUSIONS: These data implicate the RANTES-403A allele as a risk factor for HIV transmission and as a protective factor for HIV progression.
Yasuhiko Makino - One of the best experts on this subject based on the ideXlab platform.
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impaired t cell function in RANTES deficient mice
Clinical Immunology, 2002Co-Authors: Yasuhiko Makino, Donald N Cook, Oliver Smithies, Olivia Y Hwang, Eric G Neilson, Laurence A Turka, Hiroshi Sato, Andrew D Wells, Theodore M DanoffAbstract:Abstract The chemokine RANTES is a chemoattractant for monocytes and T cells and is postulated to participate in many aspects of the immune response. To evaluate the biological roles of RANTES in vivo, we generated RANTES-deficient (−/−) mice and characterized their T cell function. In cutaneous delayed-type hypersensitivity assays, a 50% reduction in ear and footpad swelling was seen in −/− mice compared to +/+ mice. In vitro, polyclonal and antigen-specific T cell proliferation was decreased. Quantitative analysis using the fluorescent dye carboxy-fluorescein succinimidyl ester revealed that this proliferative defect was due both to fewer antigen-reactive T cells and to a reduction in the capacity of these cells to proliferate. In addition, IFN-γ and IL-2 production by the −/− T cells was dramatically decreased. Together, these data suggest that RANTES is required for normal T cell functions as well as for recruiting monocytes and T cells to sites of inflammation.
Yutaka Takebe - One of the best experts on this subject based on the ideXlab platform.
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polymorphism in RANTES chemokine promoter affects hiv 1 disease progression
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: David M Chao, Emi E Nakayama, Hitomi Taguchi, Mieko Goto, Junki Takamatsu, Hidehiko Saito, Yoshihide Ishikawa, Tatsuya Akaza, Takeo Juji, Yutaka TakebeAbstract:RANTES (regulated on activation normal T cell expressed and secreted) is one of the natural ligands for the chemokine receptor CCR5 and potently suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Previous studies showed that peripheral blood mononuclear cells or CD4+ lymphocytes obtained from different individuals had wide variations in their ability to secrete RANTES. These findings prompted us to analyze the upstream noncoding region of the RANTES gene, which contains cis-acting elements involved in RANTES promoter activity, in 272 HIV-1-infected and 193 non-HIV-1-infected individuals in Japan. Our results showed that there were two polymorphic positions, one of which was associated with reduced CD4+ lymphocyte depletion rates during untreated periods in HIV-1-infected individuals. This mutation, RANTES−28G, occurred at an allele frequency of ≈17% in the non-HIV-1-infected Japanese population and exerted no influence on the incidence of HIV-1 infection. Functional analyses of RANTES promoter activity indicated that the RANTES−28G mutation increases transcription of the RANTES gene. Taken together, these data suggest that the RANTES−28G mutation increases RANTES expression in HIV-1-infected individuals and thus delays the progression of the HIV-1 disease.
Theodore M Danoff - One of the best experts on this subject based on the ideXlab platform.
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impaired t cell function in RANTES deficient mice
Clinical Immunology, 2002Co-Authors: Yasuhiko Makino, Donald N Cook, Oliver Smithies, Olivia Y Hwang, Eric G Neilson, Laurence A Turka, Hiroshi Sato, Andrew D Wells, Theodore M DanoffAbstract:Abstract The chemokine RANTES is a chemoattractant for monocytes and T cells and is postulated to participate in many aspects of the immune response. To evaluate the biological roles of RANTES in vivo, we generated RANTES-deficient (−/−) mice and characterized their T cell function. In cutaneous delayed-type hypersensitivity assays, a 50% reduction in ear and footpad swelling was seen in −/− mice compared to +/+ mice. In vitro, polyclonal and antigen-specific T cell proliferation was decreased. Quantitative analysis using the fluorescent dye carboxy-fluorescein succinimidyl ester revealed that this proliferative defect was due both to fewer antigen-reactive T cells and to a reduction in the capacity of these cells to proliferate. In addition, IFN-γ and IL-2 production by the −/− T cells was dramatically decreased. Together, these data suggest that RANTES is required for normal T cell functions as well as for recruiting monocytes and T cells to sites of inflammation.