Recombinant Human Soluble CD4 Does Not Inhibit Immune Function in Cynomolgus Monkeys

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Abstract
Recombinant soluble CD4 (sT4) has been shown to inhibit infectivity of HIV. Because of the role CD4 plays in the interaction of T-helper lymphocytes and cells bearing MHC Class II antigens, a potential adverse effect of therapy with sT4 is interference with lymphocyte function. To address this issue, we studied the effects of sT4 on mitogen-mediated blastogenesis, mixed lymphocyte reactions, and delayed type hypersensitivity reactions (DTH) in cynomolgus monkeys. We found no evidence of sT4-mediated suppression on the in vitro response to concanavalin A, phytohemagglutinin or pokeweed mitogen in 2-way mixed lymphocyte reactions, either when sT4 was added to the cultures or when cells were obtained 3 hr after drug administration from animals that received up to 100 mg/kg as an intravenous bolus. Furthermore, we also found no effect of sT4 on lymphocyte subsets or on the ability of monkeys to respond to dinitrochlorobenzene (DNCB)-mediated DTH. Because of the high degree of conservation of CD4 and MHC Class II antigens across the macaque-human barrier, these data suggest that soluble CD4-like molecules are unlikely to be immunosuppressive in humans.