Interferon-<i>γ</i>secretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma:<i>In vitro</i>stimulus determines cytokine production

Biller, Heike; Bade, Britta; Matthys, H; Luttmann, Werner; Virchow, J. Christian

doi:10.1046/j.1365-2249.2001.01666.x

Cited by 13 publications

(8 citation statements)

References 45 publications

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“…However, in contrast to that observed for CD4 + T cells, the presence of a Th2 response shift was already discernible as a drop in the percentage of CD8 + T cells producing IFN‐γ. This later observation confirms previous reports describing diminished IFN‐γ production by CD8 + T‐cells during allergic asthma (51–54). In contrast, recent reports have also described an enhancement of IFN‐γ production by CD8 + T‐cells during allergic asthma (55,56) which most likely reflects differences in methodology and disease staging (55).…”

Section: Discussionsupporting

confidence: 91%

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma

Grob

Schmid‐Grendelmeier

Joller‐Jemelka³

et al. 2003

Allergy

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Background: The ability of chemokines to regulate Th1 and Th2 responses suggests a role in the pathogenesis of atopic disorders such as allergic asthma where Th2 response dominance has been observed. Although the impact of allergic asthma on local chemokine production in the lung has been the subject of investigation, little is know about the influence of disease progression on peripheral chemokine production. We now report use of whole blood culture and flow cytometry to assess the influence of mild allergic asthma on peripheral T‐cell chemokine expression. Methods: Study participants included patients with mild allergic asthma (n = 7) and nonasthmatic controls (n = 7). Following in vitro stimulation of peripheral venous blood with phorbol 12‐myristate acetate (PMA) and ionomycin, flow cytometry was used to estimate the percentage of CD4+ and CD8+ T cells producing a number of chemokines, including macrophage inflammatory proteins MIP‐1α and MIP‐1β, RANTES (regulated on activation, T‐cell expressed and secreted), monocytic chemotactic protein‐1 (MCP)‐1, and interleukin (IL)‐8, or the cytokines interferon (IFN)‐γ and IL‐4. Serum levels of MIP‐1α, MIP‐1β, RANTES, MCP‐1, IL‐8, IFN‐γ and IL‐4 were also assessed by quantitative ELISA. Results: Intracellular expression of MIP‐1β by CD4+ and CD8+ T cells from allergic asthmatics was significantly reduced in comparison to that observed for nonasthmatics (median = 2.29% (1.75–3.50) vs 4.57% (3.38–6.64), P = 0.05; 14.20% (13.18–17.88) vs 44.10% (30.38–48.70), P = 0.01). Similarly, intracellular expression of MIP‐1α by CD8+ T cells from allergic asthmatics was also significantly lower (3.67% (1.17–5.42) vs 17.10% (4.97–20.43), P = 0.05). Conversely, IL‐8 expression by both CD4+ and CD8+ T cells from allergic asthmatics demonstrated significant enhancement (9.93% (7.77–11.28) vs 4.14% (3.61–7.11), P = 0.05; 8.40% (6.97–10.04) vs 4.98% (3.37–6.08), P = 0.05). Examination of intracellular IFN‐γ and IL‐4 revealed no significant difference in the expression of either cytokine by CD4+ T‐cells from allergic asthmatics and nonasthmatics. In contrast, expression of IFN‐γ was significantly reduced in CD8+ T‐cells from allergic asthmatics (24.60% (21.08–32.50) vs 48.40% (41.50–55.28), P = 0.01). Conclusions: The occurrence in mild allergic asthma of peripheral T‐cell chemokine expression suggestive of a diminished Th1 response, coinciding with marginal change in cytokine profiles indicative of a Th2 response bias, confirms the importance of chemokine involvement in the etiology of allergic asthma. The ability to use whole blood culture to estimate chemokine expression in T cell subsets may ultimately provide a practical means to evaluate disease status and to monitor early intervention therapies which target chemokines.

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Section: Discussionsupporting

confidence: 91%

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma

Grob

Schmid‐Grendelmeier

Joller‐Jemelka³

et al. 2003

Allergy

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“…This characterization is based on the division of CD4 ϩ T lymphocytes into two subsets first established by Mosmann et al (26). Th1 cells produce IL-2, IFN-␥, and tumor necrosis factor alpha and mediate immunity to viral and bacterial pathogens, whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and are involved in allergic diseases as well as in defense against parasitic infections (2). Moreover, Th1 and Th2 cells amplify and shape the immune responses that mediate protection of the host during infectious disease (16).…”

Section: Il-2] Gamma Interferon [Ifn-␥] Il-4 and Il-10) In Cd4mentioning

confidence: 99%

Assessment by Flow Cytometry of Cytokine Production in Malnourished Children

Rodrı́guez

González

Flores

et al. 2005

Clin Vaccine Immunol

101

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Malnutrition in children is associated with an increased risk of infection and death. Multiple abnormalities in the immune response, including cytokine production, in protein energy-malnourished children have been described and could account for the increased severity and frequency of infections. In this study, we used flow cytometry to investigate the effects of malnutrition on the production of cytokines ؉ and CD8 ؉ cells to produce IL-2, IFN-␥, IL-4, and IL-10 in response to stimulus. We concluded that both cytokine production and activation capacity were impaired in malnourished children. This functional impairment may be involved in the failure to develop a specific immune response and the predisposition to infection in these children.Malnutrition remains one of the most common causes of morbidity and mortality among children throughout the world (1). It is estimated that, in developing countries, more than one-quarter of all children younger than 5 years of age are malnourished (37). Malnutrition has been identified as an important risk factor for predisposition to infections leading to death (36). The strong association between malnutrition and infections has been established through epidemiologic studies conducted in several different countries. The severity of malnutrition determines the risk of death and/or severity of infections (17).Multiple abnormalities in the immune response, including T-cell number, ratio of T-cell subsets, NK cell activity, and cytokine production, have been described in connection with protein energy malnutrition. Nevertheless, results of studies investigating these topics are controversial (13,23,29). Several studies on the effects of malnutrition at the immunological level have been carried out with humans and experimental animals. These studies indicate that malnutrition decreases T-cell function, cytokine production, and the ability of lymphocytes to respond appropriately to cytokines (8,20,6).

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“…Biomarker concentrations are generally lower in the systemic circulation than they are at the site of production. For example, cytokines can be assayed in bronchoalveolar lavage fluid, sputum, plasma, peripheral mononuclear cells, or whole blood from asthma patients 47–51 . The first three matrices can be assayed directly for cytokines, whereas the latter two matrices must be stimulated to evaluate individualized cytokine production.…”

Section: Biomarker Assay Methodsmentioning

confidence: 99%

“…For example, cytokines can be assayed in bronchoalveolar lavage fluid, sputum, plasma, peripheral mononuclear cells, or whole blood from asthma patients. [47][48][49][50][51] The first three matrices can be assayed directly for cytokines, whereas the latter two matrices must be stimulated to evaluate individualized cytokine production. If the assay method has sufficient sensitivity, plasma or sputum is preferred for ease of collection and analysis.…”

Section: Choice Of Matrixmentioning

confidence: 99%

Biomarkers in Drug Discovery and Development: From Target Identification through Drug Marketing

Colburn¹

2003

The Journal of Clinical Pharma

137

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Biomarkers of disease play an important role in medicine and have begun to assume a greater role in drug discovery and development. The challenge for biomarkers is to allow earlier, more robust drug safety and efficacy measurements. Their role in drug development will continue to grow for the foreseeable future. For biomarkers to assume their rightful role, greater understanding of the mechanism of disease progression and therapeutic intervention is needed. In addition, greater understanding of the requirements for biomarker selection and validation, biomarker assay method validation and application, and clinical endpoint validation and application is needed. Biomarkers need to be taken into account while the therapeutic target is still being identified and the concept is being formulated. Biomarkers need to be incorporated into a continuous cycle that takes what is learned from the discovery and development of one series of biomarkers and translates it into the next series of biomarkers. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application, using such techniques as pharmacoepidemiology, pharmacogenetics, pharmacogenomics, and functional proteomics; bioanalytical method development and validation; disease process and therapeutic intervention assessments; and pharmacokinetic/pharmacodynamic modeling and simulation to improve and refine drug development. The potential for biomarkers in medicine and drug development will be limited by the least effective component of the processes. The team approach will minimize the potential for the least effective component to be fatal to the rest of the process. As scientific/regulatory foundations for biomarkers in medicine and drug development begin to be established, successes and applications will need to be effectively communicated with all of the stakeholders, including not only internal and external drug developers and regulators but also the medical community, to ensure that biomarkers are totally integrated into drug discovery and development as well as the practice of medicine.

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Interferon-γsecretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma:In vitrostimulus determines cytokine production

Cited by 13 publications

References 45 publications

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma

Assessment by Flow Cytometry of Cytokine Production in Malnourished Children

Biomarkers in Drug Discovery and Development: From Target Identification through Drug Marketing

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Interferon-γsecretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma:In vitrostimulus determines cytokine production

Cited by 13 publications

References 45 publications

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4+ and CD8+ T cells in mild allergic asthma

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4+ and CD8+ T cells in mild allergic asthma

Assessment by Flow Cytometry of Cytokine Production in Malnourished Children

Biomarkers in Drug Discovery and Development: From Target Identification through Drug Marketing

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Product

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Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma

Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma