Age-dependent changes in the susceptibility to apoptosis of peripheral blood CD4+ and CD8+ T lymphocytes with virgin or memory phenotype.

Susceptibility to apoptosis changes with age and most of the available data on lymphocytes refer to mitogen stimulated cells. We studied this susceptibility in quiescent, purified CD4+ or CD8+ T cells from a group of Italian old people compared with a group of young people. We found that an apoptotic agent such as 2-deoxy-D-ribose (dRib), which acts via glutathione depletion and oxidative stress, was more effective in CD4+ T cells from young donors, while no difference was found in CD8+ T cells. On the contrary, another agent such as TNF-alpha, which acts via receptor engagement, was more effective in CD8+ T cells from old subjects, and no difference was found in CD4+ T cells. When marker of activation-memory were investigated, no difference between young and old subjects was found when dRib was used. Differently, when TNF-alpha was used, memory and activated CD4+ T cells from old donors were less sensitive than younger counterparts, while memory CD8+ T cells from old donors were more sensitive than younger counterparts. This suggests that age-related changes in susceptibility to apoptosis of resting T cells largely depend on the type of the apoptotic stimulus which is used as well as on the memory phenotype of the cells. These results may also account, at least in part, for the deep remodelling of T cell repertoire that occurs during ageing.

Risk factors for cognitive impairment in HIV-1-infected persons with different risk behaviors.

CONTEXT: Although it is well established that acquired immunodeficiency syndrome dementia complex mainly develops in patients with advanced human immunodeficiency virus 1 (HIV-1) infection and severe immunosuppression, other factors that might increase the risk of early neuropsychological abnormalities are controversial. OBJECTIVE: To identify risk factors for HIV-1-related cognitive impairment. DESIGN: Case-control study. SETTING: Division of Infectious Diseases, University of Bologna. PARTICIPANTS: We studied 272 consecutive individuals: 90 HIV-1-seronegative, 88 asymptomatic HIV-1-seropositive, and 94 symptomatic HIV-1-seropositive persons. MAIN OUTCOME MEASURES: Cognitive impairment was defined as poor performance on at least 2 of the 7 neuropsychological tests included in the battery. Cutoff scores for poor performance on a test were established as 2 or more SDs lower than the mean of the seronegative group in the corresponding risk behavior strata: injecting drug users, hemophiliacs, and other risk behaviors. The following risk factors were studied: age, sex, education, risk behaviors, HIV-1 stage, lymphocyte count, and antiretroviral therapy. RESULTS: Compared with individuals with higher levels of education, those with less than 6 years of schooling had an odds ratio (OR) of 17.2 (95% confidence interval [CI], 3.6-83.3) for cognitive impairment, independent of age, sex, disease stage, antiretroviral therapy, and risk behavior. Compared with injecting drug users, homosexual/bisexual and heterosexual participants had ORs of 9.6 (95% CI, 2.2-42.7) and 6.3 (95% CI, 2.2-18.3), respectively, for cognitive impairment. Use of antiretroviral treatment (any vs none) was associated with lower prevalence of cognitive impairment (OR, 0.1; 95% CI, 0.0-0.3). Compared with persons with high CD4+ cell counts (> or =500/microL), those with low (<200/microL) and moderate (200-499/microL) CD4+ cell counts had adjusted ORs of 8.6 (95% CI, 1.0-71.0) and 6.9 (95% CI, 1.0-48.4), respectively. The presence of prominent depressive symptoms did not change the results. CONCLUSIONS: Low educational level, low CD4+ cell count, and homosexual/bisexual and heterosexual risk behaviors are risk factors for cognitive impairment in HIV-1-seropositive persons. Antiretroviral therapy exerts a beneficial effect against cognitive impairment in symptomatic individuals. Homosexual/bisexual and heterosexual persons who survive longer are expected to be the group at highest risk for cognitive impairment. However, the protective effect of antiretroviral therapy may balance this increased risk.