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  • Meeting abstract
  • Open Access

Regulation of T cell and monocyte activation by human anergic/suppressive CD4 CD25 T cells

  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Arthritis Research & Therapy20024 (Suppl 1) :96

https://doi.org/10.1186/ar543

  • Received: 15 January 2002
  • Published:

Keywords

  • Rheumatoid Arthritis
  • Peripheral Blood Mononuclear Cell
  • Rheumatoid Arthritis Patient
  • Cytokine Production
  • Healthy Donor

Regulation of the immune response is important to avoid chronic inflammation and autoimmunity. Anergic/suppressive CD4+CD25+ T cells have been shown to be major contributors to this regulation. We have previously shown that the suppressive CD4+CD25+ T cells can suppress mitogenic and antigen-specific CD4+ T-cell responses in humans (EJI 2001, 31:1122; Immunology 2001, 104:6). In rheumatoid arthritis (RA), besides CD4+ T cells also monocytes play an important role in the disease process. Therefore we investigated whether the suppressive CD4+CD25+ T cells could affect monocyte activation as well as T-cell activation. CD4+ T cells and monocytes were isolated from peripheral blood mononuclear cells from healthy donors via MACS isolation techniques. CD4+ T cells were separated into CD4+CD25+ and CD4+CD25- T cells. T cells and monocytes were cocultured for two days without or with anti-CD3 mAb, after which proliferation, cytokine production and phenotypic markers were investigated. Coculture of monocytes with CD4+CD25- T cells in the presence of anti-CD3 mAb resulted in strong T-cell proliferation, production of cytokines (TNF-α, IFN-γ, IL-1β, IL-10), upregulated expression of HLAII, CD40 and CD80 and remaining high CD86 levels on the monocyte/macrophage. In contrast, coculture of monocytes with CD4+CD25+ T cells and anti-CD3 mAb resulted in T-cell anergy, low levels of cytokine production, reduced upregulation of HLAII, CD40 and CD80 and downregulation of CD86. We are currently investigating how this altered activation affects the antigen-presenting and/or cartilage-destructive capacity of the monocytes/ macrophages. In conclusion, we demonstrate that anergic/-suppressive CD4+CD25+ T cells can suppress – besides T-cell responses – also the activation of monocytes. Further investigation into the function of these suppressive CD4+CD25+ T cells in RA patients as well as understanding their regulatory mechanism might elucidate their potential role in the pathogenesis of RA.

Authors’ Affiliations

(1)
University Medical Center Utrecht, Utrecht, The Netherlands

Copyright

© BioMed Central Ltd 2002

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