CD8+ cytolytic T lymphocytes and the skin

Abstract: T lymphocytes show a special affinity for the skin. Although the roles played by the CD4⁺ population of T lymphocytes in immunodermatology were so far actively investigated, much less is known about the roles played in the skin by CD8⁺ cytolytic T lymphocytes (CTL). The activity of CD8⁺ CTL in the immunodermatological context, however, is likely to be most important; the immuno-biology itself of CD8⁺ CTL, moreover, although far from being fully understood, shows intriguing characteristics. Immunophenotype, function and cytokine profile of CD8⁺ CTL are overviewed in the first section of this review. Phenotypically, not only CD8⁺ CTL can be subdivided into CD8⁺ CD28⁺ CD11b⁺ and CD8⁺ CD28^- CD11b⁺ subsets, but also an up-to-now undetected CD8⁺ CD28^- CD11b^- subset does exist. Functionally, not only “cytotoxic” but even “suppressor” subpopulations have been shown to exert cytolytic capabilities indeed, and “suppression” itself may be due to such a lytic capacity. According to cytokine synthesis, CD8⁺ CTL can be split into Tc1 and Tc2 subsets, each able to influence specific patterns of immune responses. The impact of CD8⁺ CTL in immunodermatology, overviewed in the second section of the current review, is crucial. The pathophysiology of inflammatory dermatoses is deeply influenced by the activity of CD8⁺ CTL: e.g., CD8⁺ CTL within psoriateic epidermis are possibly associated to the persistence of psoriatic lesions not undergoing resolution; on the other hand, in late lesions of lichen planus CD8⁺ CTL predominate, thus explaining presumably both the cytolytic attack against keratinocytes and the modulation of the inflammatory reaction up to the final resolution of the lesions; Tc1 cells are decreased in atopic dermatitis, and such a decrease can account both for IgE overproduction and for development of infections. Finally, CD8⁺ CTL can sustain against cutaneous viruses/tumors cytolytic immune responses not only of secondary but even of primary type, i.e. induced by Langerhans cells/dendritic cells either transfected or pulsed with skin virus/tumor-associated antigens, thus allowing the production of vaccines against cutaneous viral/neoplastic diseases.