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

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.

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Taams, L., van Amelsfort, J., Jacobs, K. et al. Regulation of T cell and monocyte activation by human anergic/suppressive CD4 CD25 T cells. Arthritis Res Ther 4 (Suppl 1), 96 (2002).

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