DC-memory T cell mixtures derived from the body surfaces support SIV replication. Both skin-and blood-derived DC populations promote virus replication in the presence of CD4+ T cells. We have been investigating whether DC subsets interact differently with naove versus memory T cells. Immature and mature blood DCs exposed to virus were mixed with memory or naove CD4+ T cells. Combinations of mature DCs with either naove or memory T cells support virus replication. In the presence of immature DCs and memory T cells virus replication is comparable to that seen in the presence of mature DCs. In contrast, virus production in the immature DC-naove T cell cultures exhibits a minimum 2-4 day delay. Therefore, the environment of DC-memory T cells, much like that at the mucosal surfaces of the body, is very permissive to SIV replication. Two animals were s.c. injected with in vitro SIV-infected autologous immature DCs. Both animals were coculture positive within 1 week, with peak viremia within 2 weeks. Although the viral levels in both animals declined after the initial peak, this was short-lived for one animal, as the viral load began to increase again. This animal did not develop any anti-SIV Ab and recently had to be euthanized [19 weeks post injection]. Blood and tissue samples have been collected and will be analyzed. We recently injected another two animals with DCs as well as two control animals with SIV-infected CD4+ T cells. All animals receiving infected DCs have become rapidly infected and 1 of the 2 animals that received infected T cells is coculture positive. We are awaiting bDNA data. FUNDING NIH (R01 AI40877) PUBLICATIONS Ignatius, R., F. Isdell, U. O?Doherty and M. Pope. Dendritic cells from skin and blood of macaques both promote SIV replication with T cells from different anatomical sites. Journal of Medical Primatology, 27:121-128, 1998. Hu, J., M. Pope, C. Brown, U. O?Doherty and C.J. Miller. Immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina and draining lymph nodes of rhesus monkeys. Laboratory Investigator, 78:435-451, 1998.
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