Induced CD8+FoxP3+ Treg cells in rheumatoid arthritis are modulated by p38 phosphorylation and monocytes expressing membrane tumor necrosis factor α and CD86.

OBJECTIVE: Limiting the severity of inflammation and promoting its eventual resolution are vital for protecting host tissues both in autoimmunity and chronic infection. The aim of this study was to determine the suitability of repurposing anti-CD3 monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA) by analyzing its ability to induce CD8+FoxP3+ Treg cells from peripheral blood mononuclear cells (PBMCs). METHODS: Anti-CD3 mAb was cultured with RA PBMCs to induce CD8+FoxP3+ Treg cells, which were analyzed by flow cytometry to determine their phenotype. Treg cell induction was investigated via neutralization or blocking antibodies, cellular depletion, or ImageStream technology. Blotting was used to determine the signaling pathways involved in CD8+FoxP3+ Treg cell induction. Suppression of CD4+ T cell effector responses was assessed by Treg cell suppression assays and Mosaic enzyme-linked immunosorbent assay. RESULTS: Potent CD8+FoxP3+ Treg cells were induced from RA PBMCs by anti-CD3 mAb. Unlike their CD4+ counterparts, CD8+FoxP3+ Treg cells inhibited Th17 responses in a contact-dependent manner, thereby functioning to limit a wider range of inflammatory pathways. CD8+FoxP3+ Treg cell induction was supported both by p38 phosphorylation intrinsic to naive CD8+ T cells and by monocytes via CD86 and membrane tumor necrosis factor α (TNFα). Artificially increasing monocyte membrane TNFα or inhibiting CD8+ T cell p38 phosphorylation drove FoxP3 expression in a subset of initially unresponsive CD8+ T cells. CONCLUSION: These data define an unknown mechanism of CD8+FoxP3+ Treg cell induction by anti-CD3 mAb, which could be combined with a p38 inhibitor to improve therapeutic efficacy in RA patients and resolve chronic inflammation via the restoration of tolerance.

Highlights on corticospinal damage and movement control from the commemorative symposium honoring the retirement of Professor Roger Lemon.

A symposium entitled "Motor control: from the periphery to the cortex and back' was held at the University College London Institute of Neurology to commemorate the retirement of Professor Roger Lemon, whose research has significantly advanced the field of fine motor cortical control. This report focuses on discussions at the symposium regarding the descending tracts associated with motor control, highlighting the neurological response and subsequent rehabilitation of motor pathway damage resulting from cerebrovascular insults.

Advances on regulatory T cells from the 15th International Congress of Immunology.

The International Congress of Immunology is the largest congregation of immunologists and meets every three years. This year, the congress was held in Milan and included talks on both basic and translational aspects of immunology. Talks on the field of regulatory T cell biology and function are highlighted in this report.