Significantly skewed memory CD8+ T cell subsets in HIV-1 infected infants during the first year of life.

HIV-1 infection causes a severe T cell compromise; however, little is known about changes in naive, memory, effector and senescent T cell subsets during the first year of life. T cell subsets were studied over the first year of life in blood from 3 infant cohorts: untreated HIV-infected, HIV-exposed but uninfected, and HIV-unexposed. In HIV-infected infants, the frequency of CCR7(+)CD45RA(+) naive CD8(+) T cells was significantly decreased, while the frequency of CCR7(-)CD45RA(-) effector memory CD8(+) T cells was increased, compared with the control cohorts. A larger population of CD8(+) T cells in HIV-infected infants displayed a phenotype consistent with senescence. Differences in CD4(+) T cell subset frequencies were less pronounced, and no significant differences were observed between exposed and unexposed HIV-uninfected infants. We concluded that the proportion of naive, memory, effector and senescent CD8(+) T cells during the first year of life is significantly altered by HIV-1 infection.

HIV-1 infection in infants severely impairs the immune response induced by Bacille Calmette-Guérin vaccine.

BACKGROUND: Worldwide, most infants born to mothers infected with human immunodeficiency virus (HIV) receive bacille Calmette-Guérin (BCG) vaccine. Tuberculosis is a major cause of death among infants infected with HIV in sub-Saharan Africa, and it should be prevented. However, BCG may itself cause disease (known as "BCGosis") in these infants. Information regarding the immunogenicity of BCG is imperative for the risk/benefit assessment of BCG vaccination in HIV-infected infants; however, no such data exist. METHODS: We compared BCG-induced CD4 and CD8 T cell responses, as assessed by flow cytometry, in HIV-infected (n=20), HIV-exposed but uninfected (n=25), and HIV-unexposed (n=23) infants, during their first year of life. RESULTS: BCG vaccination of the 2 HIV-uninfected groups induced a robust response, which was characterized by CD4 T cells expressing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and/or interleukin (IL)-2. In contrast, HIV-infected infants demonstrated a markedly lower response throughout the first year of life. These infants also had significantly reduced numbers of polyfunctional CD4 T cells coexpressing IFN-gamma, TNF-alpha, and IL-2, a finding that is thought to indicate T cell quality. CONCLUSIONS: Infection with HIV severely impairs the BCG-specific T cell response during the first year of life. BCG may therefore provide little, if any, vaccine-induced benefit in HIV-infected infants. Considering the significant risk of BCGosis, these data strongly support not giving BCG to HIV-infected infants.