Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis

• Verfasst von: Marinaki, Smaragdi [VerfasserIn]
• Verfasst von: Neumann, Irmgard [VerfasserIn]
• Verfasst von: Kälsch, Anna-Isabelle [VerfasserIn]
• Verfasst von: Grimminger, Peter [VerfasserIn]
• Verfasst von: Breedijk, Annette [VerfasserIn]
• Verfasst von: Birck, Rainer [VerfasserIn]
• Verfasst von: Schmitt, Wilhelm [VerfasserIn]
• Verfasst von: Waldherr, Rüdiger [VerfasserIn]
• Verfasst von: Yard, Benito A. [VerfasserIn]
• Verfasst von: Woude, Fokko J. van der [VerfasserIn]
• Titel: Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis
• Verf.angabe: 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
• Jahr: 2005
• Umfang: 11 S.
• Fussnoten: Gesehen am 25.05.2022
• Titel Quelle: Enthalten in: Clinical & experimental immunology
• Ort Quelle: Oxford : Wiley-Blackwell, 1966
• Jahr Quelle: 2005
• Band/Heft Quelle: 140(2005), 1, Seite 181-191
• ISSN Quelle: 1365-2249
• DOI: doi:10.1111/j.1365-2249.2005.02731.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adult
• Sach-SW: Aged
• Sach-SW: Aged, 80 and over
• Sach-SW: Antibodies, Antineutrophil Cytoplasmic
• Sach-SW: CD4-Positive T-Lymphocytes
• Sach-SW: Cells, Cultured
• Sach-SW: DNA-Binding Proteins
• Sach-SW: Female
• Sach-SW: Forkhead Transcription Factors
• Sach-SW: Humans
• Sach-SW: Immunophenotyping
• Sach-SW: Interferon-gamma
• Sach-SW: Interleukins
• Sach-SW: Kidney
• Sach-SW: Kidney Transplantation
• Sach-SW: Leukocyte Common Antigens
• Sach-SW: Lymphocyte Activation
• Sach-SW: Male
• Sach-SW: Middle Aged
• Sach-SW: Receptors, Interleukin-2
• Sach-SW: RNA, Messenger
• Sach-SW: Vasculitis
• K10plus-PPN: 1804388351

Abstract

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.