CD8+Foxp3+ T cells share developmental and phenotypic features with classical CD4+Foxp3+ regulatory T cells but lack potent suppressive activity

Abstract

"Suppressor T cells" were historically defined within the CD8+ T-cell compartment and recent studies have highlighted several naturally occurring CD8+Foxp3- Treg populations. However, the relevance of CD8+Foxp3+ T cells, which represent a minor population in both thymi and secondary lymphoid organs of nonmanipulated mice, remains unclear. We here demonstrate that de novo Foxp3 induction in peripheral CD8+Foxp3- T cells is counter-regulated by DC-mediated co-stimulation via CD80/CD86. CD8+Foxp3+ T cells fail to develop in TCR-transgenic mice with Rag1-/- background, similar to classical CD4+Foxp3+ Tregs. Notably, both naturally occurring and induced CD8+Foxp3+ T cells express bona fide Treg markers including CD25, GITR, CTLA4 and CD103, and show defective IFN-γ production upon restimulation when compared with their CD8+Foxp3- counterparts. However, utilizing DEREG transgenic mice for the isolation of Foxp3+ cells by eGFP reporter expression, we demonstrate that induced CD8+Foxp3+ T cells similar to activated CD8+Foxp3- T cells only mildly suppress T-cell proliferation and IFN-γ production. We therefore categorize CD8+Foxp3+ T cells as a tightly controlled population sharing certain developmental and phenotypic properties with classical CD4+Foxp3+ Tregs, but lacking potent suppressive activity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.