IMMUNOREGULATORY EVENTS IN THE SKIN OF PATIENTS WITH CUTANEOUS T-CELLLYMPHOMA

Background: Involved skin of patients with cutaneous T-cell lymphoma, mycosis fungoides type, contains an increased number of bone marrow-de rived epidermal cells that express class II major histocompatibility c omplex molecules and an infiltrate of both activated nonmalignant and malignant T cells. However, the mechanism by which the T cells achieve and maintain their activated state is uncertain. The aim of this arti cle is, therefore, to review recent studies from the literature dealin g with immunoregulatory events in patients with mycosis fungoides and Sezary syndrome. Observations: The nonmalignant T cells seem to be act ivated through the T-cell receptor by lesional epidermal CD1a(+)CD36() macrophagelike cells that, on a cell per cell basis, are more potent antigen-presenting cells than normal CD1a(+) Langerhans' cells presen t in uninvolved epidermis. In contrast, the malignant T cells have dif ferent activation requirements, because they can only be stimulated th rough antigen independent pathways, such as CDw60, CD28, and CD2. The malignant T cells produce T-helper (Th)-2 cytokines, and because inter feron gamma (IFN-gamma)-producing Th1 cells are present in the early l esions of mycosis fungoides, nonmalignant tumor-infiltrating T cells m ay represent Th1 cells. Because Th1 cytokines counteract Th2 cytokines , tumorinfiltrating T cells may potentially have the capacity to downr egulate the growth of the malignant cells. Conclusion: The balance bet ween progression vs remission in mycosis fungoides is related to compl ex interactions between the malignant T cells, nonmalignant T cells, a nd hyperstimulative antigen-presenting cells present within the skin.