T-cell growth factor (TCGF), also known as interleukin-2 (IL-2), is a lymphokine elaborated by one subset of lectin- or antigen-activated T-lymphocytes that supports the long-term growth of another subset of activated T lymphocytes. HUTlO2, a cell line of mature T-cell phenotype from a patient with cutaneous T-cell leukemia, produces two distinct species of TCGF (Leukemic- or L-TCGF), both of which differ physiochemically, biochemically, and antigenically from that produced by nonmalignant, lectin-stimulated human lymphocytes (normal- or N-TCGF). Although biochemical evidence implies that these L-TCGFs may be members of a new gene family with products active on T cells, their biological significance remains unclear. They may represent normal regulatory molecules whose production by this cell type has been amplified as an epiphenomenon of malignant transformation. Or they may, in a manner analogous to the epidermal growth factor-transforming, growth factor system described in murine sarcoma, virus-transformed cells, be intimately involved in the maintenance of malignant growth via an """"""""autocrine"""""""" mechanism, where the binding back of an aberrantly produced growth factor to the surface of the cell producing it, drives the cell to uncontrolled growth. To clarify these questions, studies of the comparative biological properties of N- and L-TCGF will be performed. Effects of long-term growth of these factors on phenotyplc and functional properties of T cells will be determined by FACS monoclonal antibody analysis and direct measurement of """"""""helper"""""""" or """"""""suppressor"""""""" activity. Isolated T-cell subsets will be prepared and tested for ability to grow with each factor. The marked disparity between the action of L-TCGF on PHA-stimulated human lymphocytes and mouse-cloned cytotoxic lymphocytes will be examined, and adsorption studies will be conducted with these cells to determine whether L- and N-TCGF act at the same or different receptors. Attempts will be made to purify and radiolabel the two L-TCGF species for use in receptor binding studies designed to investigate the kinetics of binding. The L-TCGF receptor will be identified by covalent binding of radiolabeled factor using a bifunctional crosslinking reagent. Finally, the ability of L-TCGF to bind the fresh leukemic cells and enhance their growth in culture will be studied. (HF)
