Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease

Peter Szodoray, Britt Nakken, S. Baráth, J. Gaál, M. Aleksza, M. Zeher, S. Sipka, Anna Szilagyi, Eva Zold, G. Szegedi, E. Bodolay

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Abstract

The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6% of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFNγ+ Th1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFNγ and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFNγ and the observed decrease of Foxp3+ Tregs. The shift toward Th1 with increased IFNγ production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.

Original languageEnglish
Pages (from-to)971-979
Number of pages9
JournalInternational Immunology
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2008

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Connective Tissue Diseases
Regulatory T-Lymphocytes
T-Lymphocytes
Interleukin-10
Hospital Distribution Systems
Cytokines
Natural Killer T-Cells
T-Lymphocyte Subsets
Flow Cytometry
B-Lymphocytes
Enzyme-Linked Immunosorbent Assay

Keywords

  • Clinical signs
  • Cytokines
  • Definitive connective tissue diseases
  • Regulatory T cells
  • Undifferentiated connective tissue disease

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease",
abstract = "The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6{\%} of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFNγ+ Th1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFNγ and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFNγ and the observed decrease of Foxp3+ Tregs. The shift toward Th1 with increased IFNγ production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.",
keywords = "Clinical signs, Cytokines, Definitive connective tissue diseases, Regulatory T cells, Undifferentiated connective tissue disease",
author = "Peter Szodoray and Britt Nakken and S. Bar{\'a}th and J. Ga{\'a}l and M. Aleksza and M. Zeher and S. Sipka and Anna Szilagyi and Eva Zold and G. Szegedi and E. Bodolay",
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T1 - Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease

AU - Szodoray, Peter

AU - Nakken, Britt

AU - Baráth, S.

AU - Gaál, J.

AU - Aleksza, M.

AU - Zeher, M.

AU - Sipka, S.

AU - Szilagyi, Anna

AU - Zold, Eva

AU - Szegedi, G.

AU - Bodolay, E.

PY - 2008/8

Y1 - 2008/8

N2 - The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6% of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFNγ+ Th1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFNγ and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFNγ and the observed decrease of Foxp3+ Tregs. The shift toward Th1 with increased IFNγ production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.

AB - The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6% of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFNγ+ Th1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFNγ and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFNγ and the observed decrease of Foxp3+ Tregs. The shift toward Th1 with increased IFNγ production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.

KW - Clinical signs

KW - Cytokines

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KW - Regulatory T cells

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