The aim of this research is to study the physiological role and the immunotherapeutic potential of the T-cell-derived immunoregulatory lymphokine, T-cell growth factor (TCGF), also known as interleukin-2 (IL-2), and to develop immunoassays for detection of IL-2 in biological fluids or lymphoid cells. To achieve these goals, we have prepared antibodies against: (1) short, chemically-synthesized peptides constructed on the basis of the predicted amino acid sequence of human lL-2; and (2) pure human recombinant IL-2 (rIL-2) made available to us by Amgen. Several antibodies against synthetic IL-2 peptides were found to react with native IL-2 by several criteria, including the high titered and specific reactivity with pure rIL-2 in enzyme-linked immunosorbent assays or immunoblots. Moreover, some of these antibodies specifically stain activated human T-cell cytoplasm and, when immobilized on plastic plates, can bind IL-2 in solution, which indicates their usefulness for developing quantitative IL-2 immunoassays. Polyclonal and monoclonal antibodies were also raised against human rIL-2 and are highly reactive with IL-2, inhibit its biological activity, and can be used to affinity-purify IL-2 from crude culture supernatants. We are also planning to use the antibodies raised against rIL-2 or synthetic IL-2 peptides in conjunction with such peptides to study the structure-function relationship of this lymphokine. Finally, the studies are in progress to evaluate the in vivo immunostimulating potential of pure IL-2 in several experimental models characterized by deficient T-cell responses, e.g., athymic nude mice, drug (cyclophosphamide, cyclosporin A)-induced immunosuppression, and tumor-bearing mice. It is hoped that these studies will elucidate the physiological role of IL-2 in the immune responses, its immunotherapeutic potential, and the role that defects in IL-2 production and response play in various immunological diseases. (TA)
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