Advancements on phenotypic and functional characterization of non–antigen-specific CD8+CD28− regulatory T cells

Among the different regulatory T lymphocyte (Treg) subpopulations, non–antigen-specific CD8+CD28− Treg (CD8+CD28− Treg) have been characterized for being involved in the pathogenesis of autoimmune diseases and cancer. A better phenotypic and functional characterization of this regulatory T-cell subset could help in identifying modulators of their activity with therapeutic finalities. The results of the present work show that Foxp3, a transcriptional marker of natural CD4+CD25+ Treg, is not expressed by CD8+CD28− Treg, thus indicating different origin and pathways of function for the latter with respect to the former regulatory cell type. Moreover, the results underline that the glucocorticoid induced TNF receptor is involved in generation processes but not in suppressor function of CD8+CD28− Treg. Phenotypic analyses demonstrate that, during their commitment from circulating nonregulatory CD8+CD28− T lymphocytes to Treg (an interleukin-10–dependent process), these cells downmodulate the IL7-receptor, thus differentiating them from long-lived, memory CD8+ T lymphocytes. Interestingly, CD8+CD28− Treg have been found to be resistant to the inhibitory effects of methylprednisolone, one of the most frequently administered corticosteroid drug used in therapy for immunosuppressive purposes.