2′, 3′-Dideoxyinosine Inhibits the Humoral Immune Response in Female B6C3F1 Mice by Targeting the B Lymphocyte
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1997/08/01
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Description:2',3'-Dideoxyinosine (ddI) is a purine nucleoside analog currently being used for the treatment of HIV-positive individuals and patients with AIDS. Preliminary immunotoxicity studies have shown that a consequence of ddI treatment in female B6C3F1 mice is the inhibition of the humoral immune response. This effect was dose dependent in a range of 100 to 1000 mg/kg with a no observed adverse effect level of less than 100 mg/kg for a 28-day treatment period. These studies were undertaken to investigate the immune cell target of ddI and to determine the mechanism of this toxicity. B6C3F1 mice were treated with 1000 mg/kg/day by oral gavage for 28 days. The B lymphocyte was identified as the cellular target of ddI through separation-reconstitution experiments of the adherent and nonadherent cell populations and of the T and B lymphocyte populations. These studies revealed a deficit in the ability of the nonadherent cells from ddI-treated mice to mount a normal antibody response to sRBC. A further separation of the nonadherent cells into T and B cells revealed a decreased ability of ddI-treated B cells to develop specific humoral immunity. Additional studies were undertaken to determine the mechanism by which ddI is affecting the B cell. Surface marker analysis of splenocytes revealed no difference in the cell populations between vehicle- and ddI-treated mice. B cell proliferation was also unaffected as shown by incubation with either a polyclonal stimulator, lipopolysaccharide, or anti-IgM plus IL-4. These results indicate that the primary cellular target of ddI is the B lymphocyte. [Description provided by NIOSH]
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ISSN:0041-008X
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Pages in Document:260-267
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Volume:145
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Issue:2
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NIOSHTIC Number:nn:20033926
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Citation:Toxicol Appl Pharmacol 1997 Aug; 145(2):260-267
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Contact Point Address:Albert E. Munson, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, Morgantown, WV 26505
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Federal Fiscal Year:1997
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Peer Reviewed:True
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Source Full Name:Toxicology and Applied Pharmacology
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Main Document Checksum:urn:sha-512:32ff6764a888e1c019d030b1544855748289c2e77e28824424fbbabddb0d536f9d65d47312f37f8b8002de0ea1267399e455c70e60b93441fb38ff12bc04b3cd
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