Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients

Giovanna Fabio, Marina Zarantonello, Cristina Mocellin, Paola Bonara, Chiara Corengia, Silvia Fargion, Gemino Fiorelli

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background/Aims: Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8+ and CD4+ T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects. Methods: Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3+CD8+ and CD3+CD4+ subsets. Results: The patients studied showed a significant decrease of total lymphocyte count, T CD4+CD3+, CD28+, CD8+CD28+ lymphocytes and natural killer (NK) CD56+CD16+CD3- cells. The reduction of CD28+ and CD8+CD28+ lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3+CD8+ subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population. Conclusions: The association of a decreased number of T CD8+ cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.

Original languageEnglish
Pages (from-to)753-761
Number of pages9
JournalJournal of Hepatology
Volume37
Issue number6
DOIs
Publication statusPublished - Dec 1 2002

Fingerprint

Hemochromatosis
Lymphocytes
Cytokines
Lymphocyte Count
T-Lymphocytes
Interleukin-4
Interleukin-10
Interleukin-13
Interleukin-5
Lymphocyte Subsets
Cytotoxic T-Lymphocytes
Transferrin
Natural Killer Cells
Interferon-gamma
Interleukin-2
Flow Cytometry
Tumor Necrosis Factor-alpha
Phenotype
Incidence
Population

Keywords

  • Hereditary hemochromatosis
  • Intracellular cytokines
  • NK cells
  • T cytotoxic cells
  • T-cytotoxic 2 cells

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients. / Fabio, Giovanna; Zarantonello, Marina; Mocellin, Cristina; Bonara, Paola; Corengia, Chiara; Fargion, Silvia; Fiorelli, Gemino.

In: Journal of Hepatology, Vol. 37, No. 6, 01.12.2002, p. 753-761.

Research output: Contribution to journalArticle

Fabio, G, Zarantonello, M, Mocellin, C, Bonara, P, Corengia, C, Fargion, S & Fiorelli, G 2002, 'Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients', Journal of Hepatology, vol. 37, no. 6, pp. 753-761. https://doi.org/10.1016/S0168-8278(02)00276-3
Fabio, Giovanna ; Zarantonello, Marina ; Mocellin, Cristina ; Bonara, Paola ; Corengia, Chiara ; Fargion, Silvia ; Fiorelli, Gemino. / Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients. In: Journal of Hepatology. 2002 ; Vol. 37, No. 6. pp. 753-761.
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AU - Fabio, Giovanna

AU - Zarantonello, Marina

AU - Mocellin, Cristina

AU - Bonara, Paola

AU - Corengia, Chiara

AU - Fargion, Silvia

AU - Fiorelli, Gemino

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AB - Background/Aims: Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8+ and CD4+ T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects. Methods: Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3+CD8+ and CD3+CD4+ subsets. Results: The patients studied showed a significant decrease of total lymphocyte count, T CD4+CD3+, CD28+, CD8+CD28+ lymphocytes and natural killer (NK) CD56+CD16+CD3- cells. The reduction of CD28+ and CD8+CD28+ lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3+CD8+ subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population. Conclusions: The association of a decreased number of T CD8+ cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.

KW - Hereditary hemochromatosis

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KW - NK cells

KW - T cytotoxic cells

KW - T-cytotoxic 2 cells

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