We are focused on human immunology, Immune Dysregulation in HIV infection, the pathogenesis of persistent viral infections (such as HIV, HCV, HBV and CMV), the determinants of inflammation in cardiovascular disease, and the mechanisms of immune homeostasis in human disease. The Laboratory of Interesting Immunology has a particular interest in utilizing randomized interventions and other clinical trial designs to elucidate immunologic mechanisms of disease pathogenesis.
IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. During untreated HIV-1 infection, levels of IL-15 increase in the LNs, inducing bystander activation of CD8 T cells and expanding HIV-1–reactive and other memory CD8 T cells (e.g., CMV specific). Following ART intervention, levels of HIV-1 fall, as do levels of IL-15, but CMV antigens persist, allowing the maintenance of CMV-specific CD8 T cells previously expanded by IL-15 exposure before ART. The size of the CD8 T cell pool remains elevated even on ART as illustrated by the black circles in HIV+/CMV+ coinfected but not in HIV+/CMV– or HIV–/CMV+ patients (41). Copyright © 2016, American Society for Clinical Investigation.
SIV/SHIV Infection Triggers Vascular Inflammation, Diminished Expression of Krüppel-like Factor 2 and Endothelial Dysfunction. Endothelial Krüppel-like factor 2 (KLF2) expression is reduced in the rhesus macaque (RM) aorta infected with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV). A, Anti-KLF2 antibody staining (Ab+) of human primary endothelial nuclei was blocked by incubating with target KLF2 peptide. B, C, Paraffin sections of descending thoracic aortas of SIV/SHIV infected (B), or uninfected (C) RMs were stained with rabbit polyclonal anti-KLF2 (B, C,upper) or rabbit (Rb) immunoglobulin (IgG) control (C, lower) followed by anti-rabbit fluorescein isothyocyanate-conjugated antibody and DAPI and examined using epifluorescence microscopy (EVOSFL; Life Technologies) with a ×40 objective (inset, ×100). D, Summary data showing normalized ratios of nuclear KLF2 (green) to nuclear DAPI (blue) fluorescence from all animals. In each aortic specimen, 100 endothelial cells were examined, and the mean ratio was summarized for each SIV-infected (red), SHIV-infected (black), and uninfected (blue) animal. Data were analyzed using 2-tailed Mann–Whitney tests; *P < .005. Abbreviations: DAPI, 4',6-diamidino-2-phenylindole; EC, endothelial cell. Copyright © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.