Lymphocyte activation in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a neoplasm of CD4+ T cells that includes mycosis fungoides and its leukemic variant, Sezary syndrome. The phenotype of CTCL cells and their predilection for localizing in the skin and regional lymph nodes indicate that CTCL is a neoplasm of mature, memory helper T cells belonging to the skin-associated lymphoid tissue. Experimental evidence suggests that the mechanisms of lymphocyte activation in CTCL may involve both T-cell receptor-dependent and -independent pathways. Furthermore, recent studies of the consequences of this activation have yielded several important findings. First, a dominant T-cell clone is generally present in CTCL specimens, including the earliest histologically diagnosable cutaneous patch lesions. Second, some cases of apparent chronic dermatitis harbor dominant T-cell clones. Such cases, known as "clonal dermatitis," have been observed to develop into overt CTCL. This suggests that patients with clonal dermatitis may be at increased risk for subsequent CTCL. Third, diseases associated with CTCL, such as lymphomatoid papulosis, large-cell lymphoma, and Hodgkin disease, arise as subclones of the original CTCL tumor and thereby share its clone-specific T-cell receptor gene rearrangements. Development of these secondary lymphoproliferative disorders appears to involve somatic mutations leading to deregulation of lymphoid activation/proliferation pathways. Fourth, CD8+ tumor-infiltrating lymphocytes present within lesions of CD4+ CTCL express a phenotype consistent with activated, major histocompatibility complex-restricted, cytotoxic T-cell differentiation. They tend to be more plentiful in early-stage disease and their proportion appears to correlate positively with improved survival, suggesting that they may exert an anti-tumor host response.