purpose: The study objective was to evaluate the effects of long-term methadone use and human T-cell leukemia virus (HTLV) types I and II seropositivity on the distribution of lymphocyte subsets and on lymphocyte function as measured in vitro in intravenous drug users seronegative for human immunodeficiency virus type 1 (HIV-1). patients and methods: Anti-HIV-1-negative intravenous drug users receiving methadone maintenance therapy (n = 24) were studied in a Veterans Administration drug abuse treatment center. These subjects Were compared to 38 ageand sex-matched control subjects who did not abuse drugs. HIV-1 and HTLV serostatus was determined by repetitive enzyme-linked immunosorbent assay and confirmed by immunoblot. Lymphocyte subsets were determined by twocolor flow cytometry. Lymphocyte function was measured by proliferative response to plant mitogens and by natural killer (NK) cell-mediated cytotoxicity to a tumor cell target. results: Significant differences were seen in lymphocyte phenotype in the methadone-treated group, with elevations in the T-cell helper subset CD4+CD29+; in CD8 and CD8+I2+ cells, suppressor/cytotoxic T lymphocytes, and activated suppressor/cytotoxic T cells; and in CD2+CD26+ cells and activated total T lymphocytes. Lymphocyte function was suppressed in the methadone group, with poor responses to pokeweed mitogen and phytohemagglutinin in culture. Moreover, NK-cell cytotoxicity was significantly reduced in the methadone group. None of these immunologic differences were attributable to HTLV serostatus. conclusion: The immune abnormalities seen suggest that a clinically significant degree of immune impairment exists in methadone-treated intravenous drug users. However, these abnormalities could not be explained by the presence of other retroviruses in this HIV-1-negative study group, as there was no significant difference in immune function when HTLV-seropositive patients were compared to HTLV-seronegative subjects treated with methadone.
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