CD25+CD4+ Regulatory T Cells from the Peripheral Blood of Asymptomatic HIV-infected Individuals Regulate CD4+ and CD8+ HIV-specific T Cell Immune Responses In Vitro and Are Associated with Favorable Clinical Markers of Disease Status

Human immunodeficiency virus (HIV) disease is associated with loss of CD4+ T cells, chronic immune activation, and progressive immune dysfunction. HIV-specific responses, particularly those of CD4+ T cells, become impaired early after infection, before the loss of responses directed against other antigens; the basis for this diminution has not been elucidated fully. The potential role of CD25+CD4+ regulatory T cells (T reg cells), previously shown to inhibit immune responses directed against numerous pathogens, as suppressors of HIV-specific T cell responses was investigated. In the majority of healthy HIV-infected individuals, CD25+CD4+ T cells significantly suppressed cellular proliferation and cytokine production by CD4+ and CD8+ T cells in response to HIV antigens/peptides in vitro; these effects were cell contact dependent and IL-10 and TGF-β independent. Individuals with strong HIV-specific CD25+ T reg cell function in vitro had significantly lower levels of plasma viremia and higher CD4+: CD8+ T cell ratios than did those individuals in whom this activity could not be detected. These in vitro data suggest that CD25+CD4+ T reg cells may contribute to the diminution of HIV-specific T cell immune responses in vivo in the early stages of HIV disease

Relationship of the genes for Chediak-Higashi syndrome (beige) and the T-cell receptor [gamma] chain in mouse and man

The genetic linkage of Chediak-Higashi syndrome and its murine analog, beige (bg), to the T-cell receptor (TCR-[gamma]) [gamma] chain gene is further defined. Previous studies using recombinant inbred strains of mice demonstrated that the murine bg gene is genetically linked to a murine TCR-[gamma] gene. We report that in the mouse the frequency of recombination between these two markers is 0.025. Further, we tested the hypothesis that these two genes are linked in the human genome by analyzing restriction fragment length polymorphisms (RFLPs) in five families with children afflicted with Chediak-Higashi syndrome. In three families, RFLPs in TCR-[gamma] genes were inherited discordantly from Chediak-Higashi syndrome, demonstrating nonlinkage. We postulate that there is an evolutionary chromosomal breakpoint between the bg gene and the TCR-[gamma] gene.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26520/1/0000058.pd

Genome sequencing reveals Zika virus diversity and spread in the Americas

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests