Dataset Information

MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines.

ABSTRACT: We analyzed for the first time the expression of chemokines in subpopulations of the murine immune system at the single-cell level. We demonstrate in vitro and in a model of murine listeriosis that macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), and activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin are cosecreted to a high degree with IFN-gamma by activated individual natural killer (NK), CD8(+) T, and CD4(+) T helper 1 (Th1) cells. Functionally, ATAC and the CC chemokines cooperate with IFN-gamma in the up-regulation of CD40, IL-12, and tumor necrosis factor-alpha, molecules playing a central role in the effector phase of macrophages. Our data indicate that (i) MIP-1alpha, MIP-1beta, RANTES, and ATAC are not only chemoattractants but also coactivators of macrophages, (ii) MIP-1alpha, MIP-1beta, RANTES, and ATAC constitute together with IFN-gamma a group of "type 1 cytokines," and (iii) these cytokines act together as a functional unit that is used by NK cells in the innate phase and then "handed over" to CD8(+) T cells in the antigen-specific phase of the immune defense, thus bridging the two components of a Th1 immune reaction.

SUBMITTER: Dorner BG

PROVIDER: S-EPMC122923 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

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MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines.

Dorner Brigitte G BG Dorner Brigitte G BG Scheffold Alexander A Rolph Michael S MS Huser Martin B MB Kaufmann Stefan H E SH Radbruch Andreas A Flesch Inge E A IE Kroczek Richard A RA

Proceedings of the National Academy of Sciences of the United States of America 20020423 9

We analyzed for the first time the expression of chemokines in subpopulations of the murine immune system at the single-cell level. We demonstrate in vitro and in a model of murine listeriosis that macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), and activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin are cosecreted to a high degree with IFN-gamma by activated individual natural kill ...[more]

PMID: 11972057

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Project description:BACKGROUND: T-cell mediated immunity likely plays an important role in controlling HIV-1 infection and progression to AIDS. Several candidate vaccines against HIV-1 aim at stimulating cellular immune responses, either alone or together with the induction of neutralizing antibodies, and assays able to measure CD8 and CD4 T-cell responses need to be implemented. At present, the IFN-gamma-based ELISPOT assay is considered the gold standard and it is broadly preferred as primary assay for detection of antigen-specific T-cell responses in vaccine trials. However, in spite of its high sensitivity, the measurement of the sole IFN-gamma production provides limited information on the quality of the immune response. On the other hand, the introduction of polychromatic flow-cytometry-based assays such as the intracellular cytokine staining (ICS) strongly improved the capacity to detect several markers on a single cell level. RESULTS: The cumulative analysis of 275 samples from 31 different HIV-1 infected individuals using an ICS staining procedure optimized by our laboratories revealed that, following antigenic stimulation, IFN-gamma producing T-cells were also producing MIP-1beta whereas T-cells characterized by the sole production of IFN-gamma were rare. Since the analysis of the combination of two functions decreases the background and the measurement of the IFN-gamma+ MIP-1beta+ T-cells was equivalent to the measurement of the total IFN-gamma+ T-cells, we adopted the IFN-gamma+ MIP-1beta+ data analysis system to evaluate IFN-gamma-based, antigen-specific T-cell responses. Comparison of our ICS assay with ELISPOT assays performed in two different experienced laboratories demonstrated that the IFN-gamma+ MIP-1beta+ data analysis system increased the sensitivity of the ICS up to levels comparable to the sensitivity of the ELISPOT assay. CONCLUSION: The IFN-gamma+ MIP-1beta+ data evaluation system provides a clear advantage for the detection of low magnitude HIV-1-specific responses. These results are important to guide the choice for suitable highly sensitive immune assays and to build reagent panels able to accurately characterize the phenotype and function of responding T-cells. More importantly, the ICS assay can be used as primary assay to evaluate HIV-1-specific responses without losing sensitivity in comparison to the ELISPOT assay.

Dataset Information

MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines.

Publications

MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines.

Similar Datasets

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