NAb were preferentially found in subjects with relatively preserved T-cell function and CD4+ T-cell numbers. In these individuals, neutralizing activity against heterologous isolates increased with time. These data suggest that the capacity to produce broadly NAb is a function of the integrity of the immune system.

To establish immunologic correlates of progression to AIDS in long-term survivors of HIV-1 infection, HIV-1-specific T cell-mediated responses, together with T cell reactivity to recall antigens, were studied in frozen samples collected after 5 and 8 years of documented HIV-1 infection. Eight of 21 homosexual men, who remained asymptomatic and maintained CD4+ T cell numbers >400 cells/microl for 9 years of HIV-1 infection, progressed to AIDS (CDC 1993 definition) within 12.5 years of infection (late progressors, LPs). The remainders showed minimal deterioration of immune parameters (long-term nonprogressors, LTNPs). CD4+ T cell numbers and T cell function measured at years 5 and 8 of follow-up were comparable in the two groups. At both time points responses to recall antigens did not significantly differ between the two groups, although a significant decline of lymphoproliferative responses to Candida and tetanus toxoid was observed in LPs. Circulating HIV-1-specific cytotoxic T lymphocyte precursors were found in broad frequency ranges in both LPs and LTNPs and, similarly, no significant differences were found in comparing the breadth of serum neutralizing activity against heterologous HIV-1 primary isolates. In contrast, lymphoproliferative responses to p24gag, but not p17gag or gp160env, were detected only in LTNPs and were totally absent in LPs at both time points (p < 0.01). Our data suggest that the presence of circulating p24-specific CD4+ T cells may reflect effective viral control and be predictive of subsequent favorable clinical course in long-term asymptomatic individuals.

The TCLI locus on chromosome 14 band q32

Nonobese diabetic (NOD) mice get spontaneous diabetes with clinical and pathological manifestations similar to those seen in human type I diabetes. NOD mice will destroy transplants of treated allogeneic islet tissue by a recurrence of the disease process that destroyed the original islet tissue. This may be prevented by treatment of the animals with combined desferrioxamine and nicotinamide. Transplanted animals become normoglycemic and remain so for the duration of the treatment. This suggests that oxygen-derived free radicals may be involved in islet damage in spontaneous diabetes.

This pilot study suggests that restored viral replication after pharmacological suppression drives the immune response to HBV in chronically infected patients. Further characterization of the adaptive immunity and its regulatory mechanisms at time of therapy discontinuation appears therefore necessary in controlled trials.