IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines

IL-17-producing CD4(+) T lymphocytes (Th17) are currently considered relevant participants in the pathogenesis of psoriasis skin lesions. However, little is known about the potential role of IL-17-producing CD8(+) T cells, which are also present at the psoriatic plaque. We have addressed the functional characterization of this CD8(+) subtype of T lymphocytes from psoriasis patients. Our results show that CD8(+)IL-17(+) cells from psoriasis-inflamed skin tissue produce TNF-alpha and IFN-gamma (Th1-related cytokines) as well as IL-17, IL-21, and IL-22 (Th17-related cytokines) efficiently. A significant up-regulation of the RORC transcription factor is also observed. These cells are refractory to Tregs but show a proliferative response to anti-CD3/CD28 stimulation that is enhanced by IL-12 and IL-15. Blocking of TNF-alpha activity inhibits TCR-mediated activation and IL-17 production. CD8(+)IL-17(+) T cells are cytotoxic cells that display TCR/CD3-mediated cytotoxic abilities to kill target cells. Thus, CD8(+)IL-17(+) T cells share some key features with Th17 cells and exhibit remarkable differential abilities attributable to the CD8(+) lineage of T lymphocytes, adding new insights into the functional resources of IL-17-producing cells from human epidermis that could be of potential interest to our understanding of the pathogenesis of psoriasis. J. Leukoc. Biol. 86: 435-443; 2009.