IFN‐γ Restores HIV‐ and Non‐HIV‐Specific Cell Mediated Immune Response <i>In Vitro</i> and Its Activity is Neutralized by Antibodies from Patients with AIDS

Francesco, Maria Antonia De; Caruso, Arnaldo; Dima, Francesco; Cantalamessa, A.; Canaris, A. D.; Folghera, S; Fiorentini, Simona; Flamminio, Gigliola; Licenziati, Stefano; Peroni, L.; Gao, Jing; Garotta, Gianni; Turano, A

doi:10.1046/j.1365-3083.1996.d01-5.x

Cited by 13 publications

(7 citation statements)

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“…It is likely that the nature of mitogenic or antigenic stimulus influences not only the activation status of T cells but also their ability to undergo proliferation. Indeed PMA, which stimulates almost 100% of T cells to express CD69, does not significantly induce DNA synthesis in the absence of a calcium ionophore (5,11,15). Also, by detecting activation antigens expressed on T cells during the late-stage differentiation leading to proliferation as CD25, CD71, and HLA-DR, the percentage of positive lymphocytes and the amount of [ 3 H]thymidine incorporation were not found to correlate under any condition tested.…”

Section: Discussionmentioning

confidence: 88%

“…Successful immune response to an infectious agent depends on the activation and proliferation of appropriate immune-competent cells. The standard way to quantify in vitro cellular immune response to a microorganism is the measurement of cell proliferation as a function of tritiated [ 3 H]thymidine incorporation, after contact between cultured lymphocytes and the microorganism or its specific antigen(s) (4,5). This assay has the disadvantage of being performed on bulk cultures and, unless lymphocyte subsets are purified, it provides no information on the cell subpopulations involved in antigen recognition or bearing functional defects.…”

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confidence: 99%

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Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation

et al. 1997

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The expression of activation antigens, namely CD25, CD69, CD71, and HLA‐DR on T cells from 15 healthy individuals stimulated with different mitogens and specific antigens was evaluated by immunofluorescence assay and flow cytometric analysis and compared with cell proliferation as a function of [3H]thymidine incorporation. CD69 was the earliest expressed antigen on stimulated cells, while HLA‐DR was the latest. Regardless of the stimulus used, lymphocytes expressing CD25 and CD71 were always more numerous than cells expressing CD69 and HLA‐DR. Variations in the proportion of CD4+ and CD8+ T cells expressing each activation marker were observed with different antigenic stimuli. The expression of each activation marker showed overall agreement with the [3H]thymidine incorporation assay in discriminating between positive and negative immune response. However, no correlation was observed between the percentage of CD25‐, CD69‐, CD71‐, and HLA‐DR‐positive T cells and the amount of [3H]thymidine incorporation. Moreover, low doses of mitogens and antigens as well as short time of stimulation were sufficient to induce T cells to express activation antigens but not to proliferate. Our data show that results obtained by flow cytometry and [3H]thymidine incorporation may differ qualitatively, at least under certain conditions; this suggests that the 2 assays are complementary, and when combined, may gives a clearer understanding of events leading to efficient cell‐mediated immune response. Cytometry 27:71–76, 1997. © 1997 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation

et al. 1997

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“…Impaired proliferative response of T-lymphocytes to antigenstimulation is related to the stage of disease [193][194][195], stimulated PBMC of HIV infected patients produce lower amounts of IL-2 as well as IFN-as PBMC of healthy controls [190]. Interestingly, exogenous substitution of cytokines is able to restore the proliferative response to antigens markedly in vitro [196,197], whereas systemic administration of IFN-may rather result in an impaired proliferative response to mitogens [43]. A study performed in 1988 first showed that increased serum neopterin concentrations in HIV infected patients were associated with diminished IFN--production of lymphocytes upon stimulation in vitro [191].…”

Section: Ido and Other Ifn--mediated Pathways In The Development Of Imentioning

confidence: 99%

Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Schroecksnadel

Zangerle

Bellmann‐Weiler

et al. 2007

CDM

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Human immunodeficiency virus type 1 (HIV) infection is characterized by progressive immunodeficiency despite of an overwhelming cellular immune activation. Patients show highly elevated serum/plasma concentrations of the proinflammatory cytokine interferon-(IFN-), which induces human monocytes to form neopterin, to produce reactive oxygen species (ROS) and in parallel, to degrade tryptophan. Enhanced tryptophan degradation by the enzyme indoleamine-2, 3-dioxygenase (IDO) contributes importantly to disease progression and "complications" of HIV infection: By a subsequent impairment of protein metabolism and serotonin formation, the development of neuropsychiatric disorders and weight loss in HIV infected patients can be enforced. Furthermore, increased IDO-activation efficiently suppresses the growth and proliferation of pathogens as well as host T-cells. IDO and other IFN--mediated pathways are strongly induced in patients with HIV infection and are also linked with disease progression: Neopterin formation by GTPcyclohydrolase I sensitively reflects the stage of the disease, and determination of the pteridine in body fluids is useful to monitor the efficacy of antiretroviral therapy. Neopterin is an independent prognostic factor for the outcome of disease, and well suited to estimate the degree of immune activation in vivo and the responsiveness of immunocompetent cells to stimulation in vitro. ROS formation may contribute to the development of oxidative stress in HIV infection, resulting in depletion of antioxidants. The cause-effective role of an overwhelming Th1-type immune response together with the activation of IDO and other IFN--mediated biochemical pathways for the course of HIV infection, the development of immunodeficiency, anemia and weight loss in HIV patients is discussed.

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“…HIV may evade CTL through a number of mechanisms including generation of escape mutants, deletion or dysregulation of CD4 ϩ Th cells, and dendritic cell dysfunction (10,11). Some acquired CTL dysfunction may be mediated by defects in expression of perforin or granzyme B (12), chemokine defects (13) or Abs (14).…”

Section: Hiv Antigens Can Induce Tgf-␤ 1 -Producing Immunoregulatory mentioning

confidence: 99%

HIV Antigens Can Induce TGF-β1-Producing Immunoregulatory CD8+ T Cells

Garba

Pilcher

Bingham

et al. 2002

The Journal of Immunology

123

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HIV-infected individuals may progressively lose both HIV-specific and unrelated CTL responses despite the high number of circulating CD8+ T cells. In this study, we report that approximately 25% of HIV+ donors produced TGF-beta(1) in response to stimulation with HIV proteins or peptides. The production of TGF-beta(1) was sufficient to significantly reduce the IFN-gamma response of CD8+ cells to both HIV and vaccinia virus proteins. Ab to TGF-beta reversed the suppression. We found the source of the TGF-beta(1) to be predominantly CD8+ cells. Different peptide pools stimulated TGF-beta(1) and IFN-gamma in the same individual. The TGF-beta(1) secreting cells have distinct peptide specificity from the IFN-gamma producing cells. This represents an important mechanism by which an HIV-specific response can nonspecifically suppress both HIV-specific and unrelated immune responses.

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IFN‐γ Restores HIV‐ and Non‐HIV‐Specific Cell Mediated Immune Response In Vitro and Its Activity is Neutralized by Antibodies from Patients with AIDS

Cited by 13 publications

References 18 publications

Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation

Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation

Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

HIV Antigens Can Induce TGF-β1-Producing Immunoregulatory CD8+ T Cells

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IFN‐γ Restores HIV‐ and Non‐HIV‐Specific Cell Mediated Immune Response In Vitro and Its Activity is Neutralized by Antibodies from Patients with AIDS

Cited by 13 publications

References 18 publications

Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation

Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation

Indoleamine-2, 3-Dioxygenase and Other Interferon-&#947;-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

HIV Antigens Can Induce TGF-β1-Producing Immunoregulatory CD8+ T Cells

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Product

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Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection