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

CT Mayer, S Floess, AM Baru, K Lahl… - European journal of …, 2011 - Wiley Online Library
CT Mayer, S Floess, AM Baru, K Lahl, J Huehn, T Sparwasser
European journal of immunology, 2011Wiley Online Library
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 …
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.
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