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The present study compares the in vitro effect of (±)-2'-deoxy-3'-thiacytidine (BCH 189) a new synthetic anti-HIV-1 dideoxynucleoside, with 3'-azido-3'-deoxythymidine (AZT) on the immune function of lymphocytes from 10 normal and 12 HIV-1+ patients (CDC II and III). The effect of different doses of BCH 189 and AZT was analysed in vitro on: (i) T cell proliferation after stimulation with concanavalin A (Con A) or anti-CD3 MoAb; (ii) B cell proliferation and immunoglobulin production after stimulation with pokeweed mitogen (PWM); (iii)cytokine production (IL-2, IL-6, GM-CSF, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) from lymphocytes stimulated with anti-CD3 MoAb or phytohaemagglutinin (PHA). BCH 189 inhibited the proliferation of B and T lymphocytes from normal and HIV+ subjects less than AZT; even if lymphocytes from HIV+ (CDC III) subjects produced higher levels of IL-6 and TNF-α, neither BCH 189 nor AZT molecule interfered with cytokine release. Immunoglobulin production from B lymphocytes was inhibited only by a high concentration (50 μM) of BCH 189 or AZT. These results show that BCII 189 affects lymphocyte proliferation in vitro less then AZT, and support its use in clinical trials in HIV-infected patients. [ABSTRACT FROM AUTHOR]

The immunotoxic potential of ENU, a potent and transplacental neurocarcinogen, was evaluated in male CDI mice. The animals received i.p. injections of ENU--0, 2, 8 or 32 mg/kg body weight, in citrate-phosphate buffer, twice weekly for three weeks. Splenic lymphocytes were cultured in the presence of mitogens, lipopolysaccharide, pokeweed mitogen, concanavalin A and phytohaemagglutinin. Mixed lymphocyte cultures in the presence of allogeneic cells were also tested. Blastogenic response decreased in a dose-dependent manner, as measured by the 3H-thymidine uptake by splenocytes. Primary antibody production by splenic lymphocytes from animals challenged with a T- dependent antigen (sheep red blood cells) was stimulated at low doses but depressed at the highest dose group compared with the controls, whereas T-independent cell response showed no significant change. Our results suggest that exposure to repeated, low levels of ENU significantly alters the immune status of CD1 mice. The effects appear to be somewhat selective to T cell processes, based on in vivo responses to T-dependent and T-independent antigens. [ABSTRACT FROM AUTHOR]