Details der Publikation - Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis

Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis / S. Marinaki, I. Neumann, A.-I. Kälsch, P. Grimminger, A. Breedijk, R. Birck, W. Schmitt, R. Waldherr, B.A. Yard and F.J. Van Der Woude

In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4(+) CD25(+) T-regulatory-cells (T(reg)) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in T(reg) cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4(+) cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4(+) lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25(+) cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4(+) CD45RB(high)) population only. FOXP3 mRNA expression in CD4(+) T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P < 0.01). PBMC of AAV patients produced significantly less interleukin (IL)-10 and interferon (IFN)-gamma after anti-CD3/CD28 stimulation. The percentage of IL-10 and IL-12, but not IFN-gamma, IL-4 or tumour necrosis factor (TNF)-alpha-producing cells was significantly higher in patients compared to HC. These findings were confined to the memory population of CD4(+) cells. We conclude that AAV patients are lymphopenic and have low numbers of CD4(+) T cells, which seem to be in a persistent state of activation..

Medienart:	E-Artikel

Erscheinungsjahr:	2005
Erschienen:	2005

Enthalten in:	Zur Gesamtaufnahme - volume:140
Enthalten in:	Clinical & experimental immunology - 140(2005), 1, Seite 181-191

Sprache:	Englisch

Beteiligte Personen:	Marinaki, Smaragdi, 1970- [VerfasserIn] Neumann, Irmgard [VerfasserIn] Kälsch, Anna-Isabelle [VerfasserIn] Grimminger, Peter, 1978- [VerfasserIn] Breedijk, Annette, 1960- [VerfasserIn] Birck, Rainer, 1966- [VerfasserIn] Schmitt, Wilhelm, 1960- [VerfasserIn] Waldherr, Rüdiger [VerfasserIn] Yard, Benito A., 1961- [VerfasserIn] Woude, Fokko J. van der, 1953-2006 [VerfasserIn]

Links:	Volltext [lizenzpflichtig] Volltext [lizenzpflichtig]

Themen:	Adult Aged Aged, 80 and over Antibodies, Antineutrophil Cytoplasmic CD4-Positive T-Lymphocytes Cells, Cultured DNA-Binding Proteins Female Forkhead Transcription Factors Humans Immunophenotyping Interferon-gamma Interleukins Kidney Kidney Transplantation Leukocyte Common Antigens Lymphocyte Activation Male Middle Aged RNA, Messenger Receptors, Interleukin-2 Vasculitis

Anmerkungen:	Gesehen am 25.05.2022

Umfang:	11

doi:	10.1111/j.1365-2249.2005.02731.x

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1804388351

Internformat


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245	1	0	\|a Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis \|c S. Marinaki, I. Neumann, A.-I. Kälsch, P. Grimminger, A. Breedijk, R. Birck, W. Schmitt, R. Waldherr, B.A. Yard and F.J. Van Der Woude
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520			\|a In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4(+) CD25(+) T-regulatory-cells (T(reg)) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in T(reg) cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4(+) cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4(+) lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25(+) cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4(+) CD45RB(high)) population only. FOXP3 mRNA expression in CD4(+) T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P < 0.01). PBMC of AAV patients produced significantly less interleukin (IL)-10 and interferon (IFN)-gamma after anti-CD3/CD28 stimulation. The percentage of IL-10 and IL-12, but not IFN-gamma, IL-4 or tumour necrosis factor (TNF)-alpha-producing cells was significantly higher in patients compared to HC. These findings were confined to the memory population of CD4(+) cells. We conclude that AAV patients are lymphopenic and have low numbers of CD4(+) T cells, which seem to be in a persistent state of activation.
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650		4	\|a Leukocyte Common Antigens
650		4	\|a Lymphocyte Activation
650		4	\|a Male
650		4	\|a Middle Aged
650		4	\|a Receptors, Interleukin-2
650		4	\|a RNA, Messenger
650		4	\|a Vasculitis
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Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis / S. Marinaki, I. Neumann, A.-I. Kälsch, P. Grimminger, A. Breedijk, R. Birck, W. Schmitt, R. Waldherr, B.A. Yard and F.J. Van Der Woude

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