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A role for CD8 cells in cell-contact-mediated inflammation

Background

While the aetiology of rheumatoid arthritis (RA) is unknown, emerging data suggest that T cell:macrophage cell–cell interactions are critical in disease perpetuation. Cytokine/mitogen-activated CD4+ T cells or CD4+ T cells isolated directly from RA synovial fluid (SF) are known to induce tumour necrosis factor alpha (TNF-α) production by monocytes via a cell-contact-mediated mechanism. However, little is known about the ability of CD8+ cells to drive such effects.

Objective

To investigate the potential role of CD8+ cells in cell-contact-mediated stimulation of monocytes, via induction of cytokines. To examine whether CD8+ cells isolated from RA SF, like their CD4+ counterparts, have an inherent ability to drive monocyte activation.

Methods

CD8+ or CD4+ cells from healthy volunteer or RA peripheral blood were isolated by immunomagnetic positive selection and activated by phytohaemagglutinin, IL-15 or a cytokine cocktail (IL-6, IL-15 and TNF-α) for 3/6 days, respectively. SF T cells were purified by immunomagnetic bead separation. T cells were paraformaldehyde-fixed prior to co-culture with autologous immunomagnetically purified CD14-positive cells. CD8+/CD4+ cells isolated from RA SF were fixed without prior stimulation. Secreted cytokine production by monocytes was measured by ELISA/Luminex after 48 hours. The purity of isolated CD8+/CD4+ populations was assessed by FACS analysis and was routinely > 95%.

Results

Mitogen-activated peripheral blood CD8+ cells induced TNF-α production by monocytes in a cell-contact-dependent manner. Peripheral blood CD8+ cells previously activated by IL-15 alone or a cocktail of cytokines similarly stimulated monocyte TNF-α production. Moreover, CD8+ cells isolated directly from RA SF induced autologous monocyte TNF-α secretion in the absence of prior in vitro activation. Levels of monocyte cytokine production stimulated by CD8+ cells were comparable with levels induced by CD4+ cells in all circumstances investigated.

Conclusion

The ability of CD8+ cells to stimulate monocyte inflammatory cytokine production via a contact-dependent mechanism provides a novel means by which T-cell subsets activated within the local cytokine milieu in RA may contribute to the ongoing disease process. Further understanding of the contribution made by this population to monocyte/macrophage activation is therefore crucial.

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Robertson, S., Crilly, A., Gracie, J. et al. A role for CD8 cells in cell-contact-mediated inflammation. Arthritis Res Ther 7, P163 (2005). https://doi.org/10.1186/ar1684

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  • DOI: https://doi.org/10.1186/ar1684

Keywords

  • Rheumatoid Arthritis
  • Synovial Fluid
  • Rheumatoid Arthritis Synovial Fluid
  • Immunomagnetic Bead
  • Cytokine Cocktail