The aim of this study was to assess the efficacy and tolerance of interferon alpha (IFN alpha) treatment of chronic hepatitis C in HIV-seropositive patients. Seventeen patients with actively replicating hepatitis C were consecutively enrolled and treated with IFN alpha 5 MIU three times a week and followed up for at least 6 months after cessation of treatment. Eight patients responded to IFN alpha therapy with a complete remission of signs of active hepatitis and viral replication (ALT, HCV-RNA) at the end of treatment with IFN alpha. A sustained complete remission (ALT, HCV-RNA) for at least 6 months after the end of treatment was achieved in five of these eight patients. Complete responders had higher CD4+ cell counts (median 525/microliter) compared to non-responders (median 245/microliter) (p< 0.001). All patients but one completed at least 4 months of treatment. No severe toxicity (> WHO grade 2) due to IFN alpha treatment occurred. The results indicate that IFN alpha treatment of chronic hepatitis C in HIV-seropositive patients is successful in a considerable number of cases. Success of treatment with IFN alpha is related to higher CD4+ cell counts.
Previously we have described the induction of MHC-unrestricted killer cells against bladder tumour cells by bacillus Calmette-Guérin (BCG), termed BCG-activated killer (BAK) cells. In the present paper we deal with the accessory-cell requirement for the activation of BAK cells. We show that monocytes are required for activating BAK cells, since no cytotoxicity can be induced in the absence of monocytes. Therefore, these phagocytes may represent the first step during the activation cascade of BAK cells. Furthermore, the presence of CD4+ T cells was essential for generating BAK cells: depleting peripheral blood mononuclear cells of CD4+ cells prior to stimulation with BCG abolished the cytotoxicity against bladder tumour cells. Experiments with monoclonal antibodies (mAb) neutralizing the activity of either interleukin-2 (IL-2) or interferon gamma (IFN gamma) underlined the importance of these cytokines: both mAb blocked the induction of BAK cells. Since both cytokines are related to the so-called Th1 pattern of T cells, we consider the second step of the generation of BAK cells as follows: monocytes presenting antigens of BCG trigger Th1-like cells in a preferred manner. These Th1-like T cells secrete IL-2 and IFN gamma and, thus, activate the BAK effector cells. Since CD4+ cells are dominant in the cells infiltrating the bladder wall after intravesical instillation of BCG in vivo, we postulate an important role for the Th1 subpopulation. We further postulate that the occurrence of macrophages in this infiltrate seems to be significant in the maintenance of the relapse-free state of the patient.
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