CD8+ T suppressor cells are back to the game: are they players in autoimmunity?

The CD8+ T suppressor lymphocytes identified in humans belong to three different subpopulations. All of them inhibit the proliferation of antigen-specific T cells. The type 1 and type 2 of CD8+ T suppressor cells are characterized by the CD8+CD28− phenotype, while no detailed data are available at the moment on the phenotype of the type 3 of CD8+ T suppressor cells. The type 1 of CD8+ suppressor T lymphocytes acts by inducing alteration of expression of co-stimulatory molecules on dendritic cells. A cell-to-cell contact is required to mediate this effect. The type 2 of CD8+ T suppressor cells induces inhibition via cytokine secretion (IFNγ, IL6) and do not need to interact directly with antigen presenting cells. The type 3 of CD8+ T suppressor cells mediates its function through the secretion of IL10. The complexity and multiplicity of CD8+ T suppressor cell subsets suggests that these cells may have an important role in the regulation of the immune homeostasis, acting together with the CD4+ T regulatory cell subpopulations. The specificity of the functions of each of these suppressor/regulatory subsets in the immune network requires to be clarified to better understand the immune system, its functions and the possibilities to modulate its activities in the course of immune-mediated diseases.