IMMUNOBIOLOGY OF CUTANEOUS T CELL LYMPHOMA

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Cutaneous T-cell lymphoma (CTCL) is a malignancy of T lymphocytes, which have the functional and phenotypic properties of helper T cells. This neoplasm has an incidence approximating, and probably exceeding, that of Hodgkin's disease and regularly presents with skin lesions. The natural course of the disease involves evolution of subclones composed of more poorly differentiated T cells that have a decreased affinity for epidermis and an increased propensity to disseminate widely, leading to a median survival of less than 5 years from the time of histopathological diagnosis. These studies have two broad interrelated objectives. First, two monoclonal antibodies (BE1 and BE2), which have specificity for tumor-associated antigens of CTCL cells, will be studied in order to determine their efficacy as diagnostic and potentially therapeutic reagents. The CTCL antigens with which these and other monoclonal antibodies react will be functionally and chemically characterized to determine their relationship to other known membrane markers, as well as to human T lymphoma virus that is a suspected etiological agent for this disease. Second, the possibility that the environment of the epidermis provides a privileged site for the clonal expansion of malignant and benign helper T cells will be explored. In this context, the relationship between, and chemical properties of, two factors produced by epidermal cells (interleukin-1-like and thymopoietin-like factors) will be investigated. It is anticipated that these studies will facilitate better understanding, more efficient diagnosis, and improved therapy of CTCL and that they will also significantly contribute to our knowledge of basic human T-cell biology. (MI)