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

Among the different regulatory T lymphocyte (Treg) subpopulations, non\u2013antigen-specific CD8CD28Treg (CD8CD28 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 CD4CD25 Treg, is not expressed by CD8CD28 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 CD8CD28Treg. Phenotypic analyses demonstrate that, during their commitment from circulating nonregulatory CD8CD28 T lymphocytes to Treg (an interleukin-10\u2013 dependent process), these cells downmodulate the IL7-receptor, thus differentiating them from long-lived, memory CD8 T lymphocytes. Interestingly, CD8CD28 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