Impaired Naive and Memory B-Cell Responsiveness to TLR9 Stimulation in Human Immunodeficiency Virus Infection▿

Toll-like receptor 9 (TLR9) agonists such as unmethylated bacterial CpG DNAs activate B lymphocytes directly, potentially influencing their function and homeostasis. To assess B-cell responsiveness to TLR9 agonists in human immunodeficiency virus (HIV) disease, we examined the ability of naive and memory B cells to proliferation and to increase surface expression of CD80 in response to CpG oligonucleotides (ODN). CpG ODN induced expression of CD80 similarly in B cells from HIV-infected persons and from healthy controls. In contrast, proliferation responses to CpG ODN were markedly impaired in both naive and memory B-cell subsets from HIV-infected persons. Naive B-cell proliferation defects were related to plasma HIV RNA and, among memory B cells, to the frequencies of CD21-negative cells. Importantly, TLR9 mRNA levels were significantly diminished in freshly prepared naive B cells and especially so in memory B cells from HIV-positive viremic donors, suggesting a possible underlying mechanism for the observed functional impairments. Dose-response studies indicated that optimal induction of CD80 expression was achieved with much lower concentrations of CpG ODN than optimal induction of proliferation. We propose that the relatively low threshold of activation that is required for CD80 induction by CpG ODN might explain the preservation of this response in B cells from HIV-infected persons despite diminished TLR9 expression. Impaired responsiveness to TLR9 agonists may contribute to defects in humoral immunity in HIV infection

Childhood leukemia following the Chernobyl accident - the European Childhood Leukemia Lymphoma Incidence Study (ECLIS)

The objective of the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) is to investigate trends in incidence rates of childhood leukaemia and lymphoma in Europe, in relation to the exposure to radiation which resulted from the accident at the Chernobyl nuclear power plant in April 1986. In this first report, the incidence of leukaemia in children aged 0-14 is presented from cancer registries in 20 European countries for the period 1980-1988. Risk of leukaemia in 1987-1988 (8-32 months post-accident) relative to that before 1986, is compared with estimated average dose of radiation received by the population in 30 geographic areas. The observed changes in incidence do not relate to exposure. The period of follow-up is so far rather brief, and the study is planned to continue for at least 10 years