CLONING, ANALYSIS NON HUMAN PRIMATE CYTOKINES, IMMUNE RECEPTORS

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Recent therapeutic attempts include a variety of cytokines, hematopoietic growth factors, or specific ligands for the modulation of immune responses and hematopoiesis for the treatment of various clinical conditions or as adjuvant to immunization protocols. A significant number of such applications are studied using various nonhuman primate models, yet while most human factors appear biologically active in nonhuman primates, data shows that injection of human recombinant cytokines most often does not allow repeated or long-term treatment due to rapid development of an immune response towards these "foreign" molecules, resulting in inactivation and clearance of these cytokines. Furthermore the immune response of primate cells to the stimulation by certain human cytokines has been found to be markedly lower than the response of equivalent cells from human origins. There is a particular interest in cytokines that play a deterministic role in modulating the type of immu ne r esponse to certain pathogens including SIV. Therefore, cDNA coding for various nonhuman primate cytokines were cloned and sequenced. In addition, we have extended such analyses to new world aotus monkeys and common marmoset monkeys, as well as to old world baboons. In this regard, efforts have been devoted at expressing recombinant macaque IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, IL-16, IL-18 TNF-(, Flt-3L and IFN(. In addition Native and modified C-C Chemokines were generated as these factors may block lentivirus infection by downregulating the coreceptor for viral entry. Recombinant macaque IL-2, IL-4 and IL-12 are currently being utilized in vivo to potentiate SIV immunizations in collaboration with 2 research teams in Europe and with Dr. Vogel's research group at the NIH. IL-12 is also currently being assessed therapeutically in SIV infected macaques with Dr. Hillyer at the Yerkes Center. These studies bear the potential to rapidly translate into therapeutic applications for th e treatment of human diseases. FUNDING NIH / NIAID $21,228 8/01/98 - 7/31/99 C00 IPR Karen Kenya/Case Western University UC San Francisco, Dept of Neurobiology, Naval Medical Research Institute, Bethesda. PUBLICATIONS None