Correlation of increased susceptibility to apoptosis of CD4+ T cells with lymphocyte activation and activity of disease in patients with primary Sjogren's syndrome

M. Zeher, Péter Szodoray, E. Gyimesi, Z. Szondy

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31 Citations (Scopus)

Abstract

Objective. To investigate whether a change in the CD95-related apoptosis of T lymphocytes might have a share in the development of the disease in patients with primary Sjogren's syndrome (SS). Methods. Two-color cytometric analysis was used to study the phenotype of freshly separated mononuclear cells, while Western blotting was used to detect CD95 ligand (CD95L) expression in total homogenates of isolated CD4+ T lymphocytes. The ability of various subpopulations of T cells to undergo apoptosis was investigated in 1-day cultures in medium alone or following various (anti-CD3, anti-CD95 monoclonal antibody, calcium ionophore) treatments. Apoptosis was detected using 7-aminoactinomycin D dye. Results. Compared with the findings in healthy controls, the number of CD4+ T lymphocytes was decreased, while their expression of CD95, HLA-DR, and CD45RO was significantly increased in patients with primary SS. A positive correlation was found between the activity of disease, the decrease in the CD4+ T cell number, and the increase in the expression of CD95, CD95L, HLA-DR, and CD45RO molecules within time CD4+ T cell subset. An increased rate of spontaneous, anti-CD3-, or anti- CD95-induced apoptosis was found in the T cells of SS patients, and this was more pronounced in the CD4+ T cell population, correlated with the decreased CD4+ T cell number, increased CD45RO expression, and activity of disease, and concerned mainly the CD95+ cells. Conclusion. These observations indicate that the increased susceptibility to apoptosis of peripheral CD4+ T cells from SS patients correlates with disease activity. These findings support the hypothesis that the chronic activation of the immune system that occurs in this autoimmune disease is the primary mechanism responsible for this cell- deletion process.

Original languageEnglish
Pages (from-to)1673-1681
Number of pages9
JournalArthritis and Rheumatism
Volume42
Issue number8
DOIs
Publication statusPublished - Aug 1999

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Sjogren's Syndrome
Lymphocyte Activation
Apoptosis
T-Lymphocytes
Fas Ligand Protein
HLA-DR Antigens
Cell Count
Calcium Ionophores
T-Lymphocyte Subsets
Autoimmune Diseases
Culture Media
Immune System
Coloring Agents
Color
Western Blotting
Monoclonal Antibodies
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

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title = "Correlation of increased susceptibility to apoptosis of CD4+ T cells with lymphocyte activation and activity of disease in patients with primary Sjogren's syndrome",
abstract = "Objective. To investigate whether a change in the CD95-related apoptosis of T lymphocytes might have a share in the development of the disease in patients with primary Sjogren's syndrome (SS). Methods. Two-color cytometric analysis was used to study the phenotype of freshly separated mononuclear cells, while Western blotting was used to detect CD95 ligand (CD95L) expression in total homogenates of isolated CD4+ T lymphocytes. The ability of various subpopulations of T cells to undergo apoptosis was investigated in 1-day cultures in medium alone or following various (anti-CD3, anti-CD95 monoclonal antibody, calcium ionophore) treatments. Apoptosis was detected using 7-aminoactinomycin D dye. Results. Compared with the findings in healthy controls, the number of CD4+ T lymphocytes was decreased, while their expression of CD95, HLA-DR, and CD45RO was significantly increased in patients with primary SS. A positive correlation was found between the activity of disease, the decrease in the CD4+ T cell number, and the increase in the expression of CD95, CD95L, HLA-DR, and CD45RO molecules within time CD4+ T cell subset. An increased rate of spontaneous, anti-CD3-, or anti- CD95-induced apoptosis was found in the T cells of SS patients, and this was more pronounced in the CD4+ T cell population, correlated with the decreased CD4+ T cell number, increased CD45RO expression, and activity of disease, and concerned mainly the CD95+ cells. Conclusion. These observations indicate that the increased susceptibility to apoptosis of peripheral CD4+ T cells from SS patients correlates with disease activity. These findings support the hypothesis that the chronic activation of the immune system that occurs in this autoimmune disease is the primary mechanism responsible for this cell- deletion process.",
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T1 - Correlation of increased susceptibility to apoptosis of CD4+ T cells with lymphocyte activation and activity of disease in patients with primary Sjogren's syndrome

AU - Zeher, M.

AU - Szodoray, Péter

AU - Gyimesi, E.

AU - Szondy, Z.

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N2 - Objective. To investigate whether a change in the CD95-related apoptosis of T lymphocytes might have a share in the development of the disease in patients with primary Sjogren's syndrome (SS). Methods. Two-color cytometric analysis was used to study the phenotype of freshly separated mononuclear cells, while Western blotting was used to detect CD95 ligand (CD95L) expression in total homogenates of isolated CD4+ T lymphocytes. The ability of various subpopulations of T cells to undergo apoptosis was investigated in 1-day cultures in medium alone or following various (anti-CD3, anti-CD95 monoclonal antibody, calcium ionophore) treatments. Apoptosis was detected using 7-aminoactinomycin D dye. Results. Compared with the findings in healthy controls, the number of CD4+ T lymphocytes was decreased, while their expression of CD95, HLA-DR, and CD45RO was significantly increased in patients with primary SS. A positive correlation was found between the activity of disease, the decrease in the CD4+ T cell number, and the increase in the expression of CD95, CD95L, HLA-DR, and CD45RO molecules within time CD4+ T cell subset. An increased rate of spontaneous, anti-CD3-, or anti- CD95-induced apoptosis was found in the T cells of SS patients, and this was more pronounced in the CD4+ T cell population, correlated with the decreased CD4+ T cell number, increased CD45RO expression, and activity of disease, and concerned mainly the CD95+ cells. Conclusion. These observations indicate that the increased susceptibility to apoptosis of peripheral CD4+ T cells from SS patients correlates with disease activity. These findings support the hypothesis that the chronic activation of the immune system that occurs in this autoimmune disease is the primary mechanism responsible for this cell- deletion process.

AB - Objective. To investigate whether a change in the CD95-related apoptosis of T lymphocytes might have a share in the development of the disease in patients with primary Sjogren's syndrome (SS). Methods. Two-color cytometric analysis was used to study the phenotype of freshly separated mononuclear cells, while Western blotting was used to detect CD95 ligand (CD95L) expression in total homogenates of isolated CD4+ T lymphocytes. The ability of various subpopulations of T cells to undergo apoptosis was investigated in 1-day cultures in medium alone or following various (anti-CD3, anti-CD95 monoclonal antibody, calcium ionophore) treatments. Apoptosis was detected using 7-aminoactinomycin D dye. Results. Compared with the findings in healthy controls, the number of CD4+ T lymphocytes was decreased, while their expression of CD95, HLA-DR, and CD45RO was significantly increased in patients with primary SS. A positive correlation was found between the activity of disease, the decrease in the CD4+ T cell number, and the increase in the expression of CD95, CD95L, HLA-DR, and CD45RO molecules within time CD4+ T cell subset. An increased rate of spontaneous, anti-CD3-, or anti- CD95-induced apoptosis was found in the T cells of SS patients, and this was more pronounced in the CD4+ T cell population, correlated with the decreased CD4+ T cell number, increased CD45RO expression, and activity of disease, and concerned mainly the CD95+ cells. Conclusion. These observations indicate that the increased susceptibility to apoptosis of peripheral CD4+ T cells from SS patients correlates with disease activity. These findings support the hypothesis that the chronic activation of the immune system that occurs in this autoimmune disease is the primary mechanism responsible for this cell- deletion process.

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