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bioRxiv · 10.1101/2022.07.22.501159

PD-1 and CTLA-4 exert additive control of effector regulatory T cells

Perry, J. A.·Lanzar, Z.·Clark, J. T.·Hart, A. P.·Douglas, B. B.·Shallberg, L.·O'Dea, K.·Christian, D. A.·Hunter, C. A.
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Abstract

At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in Treg cells which was associated with increased eTreg proliferation, enhanced production of IL-10, and altered dendritic cell expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.

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Perry, J. A., Lanzar, Z., Clark, J. T., Hart, A. P., Douglas, B. B., Shallberg, L., O'Dea, K., Christian, D. A., Hunter, C. A.. 2022-07-22. PD-1 and CTLA-4 exert additive control of effector regulatory T cells. https://doi.org/10.1101/2022.07.22.501159

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