title: Recombinant human soluble CD4 does not inhibit immune function in cynomolgus monkeys.
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.
authors.affiliation: Department of Experimental Pathology, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania 19406.
authors.forename: P J
authors.initials: PJ
authors.lastname: Bugelski
authors.forename: P A
authors.initials: PA
authors.lastname: Thiem
authors.forename: A
authors.initials: A
authors.lastname: Truneh
authors.forename: D G
authors.initials: DG
authors.lastname: Morgan
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D015704:CD4 Antigens; D011994:Recombinant Proteins; C076613:recombinant soluble CD4