Basic Science Award

Sexual transmission accounts for most cases of HIV infection worldwide, with semen being the main carrier of viral particles during this process. Recent studies revealed that positively charged amyloid fibrils from human semen can substantially boost HIV infectivity rates. In two separate studies, M?nch et al. and our group identified two distinct HIV-enhancing semen amyloids.

Invariant natural killer T (NKT) cells are innate-like T cells that respond to lipid antigens presented on the MHC class I-like molecule CD1d. These immunoregulatory cells have the capacity for abundant cytokine release almost immediately after antigen recognition and are essential for the activation of multiple arms of the immune response, including dendritic cells, conventional T cells and B cells. Murine studies have shown that the intestinal microbiome is an important factor in the maturation of functional NKT cells.

Detection of gene expression by flow cytometry is currently limited to transcripts that are abundantly expressed, however the recently reported RNAscope technology offers greatly improved sensitivity and specificity and has the potential to change the approach to single-cell transcript measurements that currently require low sensitivity approaches and are extremely low throughput. As yet these probes have not been utilized for study of patient samples by flow cytometry.

Invariant natural killer T (NKT) cells are innate-like T cells that respond to lipid antigens presented on the MHC class I-like molecule CD1d. These immunoregulatory cells have the capacity for abundant cytokine release almost immediately after antigen recognition and are essential for the activation of multiple arms of the immune response, including dendritic cells, conventional T cells and B cells. Murine studies have shown that the intestinal microbiome is an important factor in the maturation of functional NKT cells.

Detection of gene expression by flow cytometry is currently limited to transcripts that are abundantly expressed, however the recently reported RNAscope technology offers greatly improved sensitivity and specificity and has the potential to change the approach to single-cell transcript measurements that currently require low sensitivity approaches and are extremely low throughput. As yet these probes have not been utilized for study of patient samples by flow cytometry.

The depletion of CD4 T cells and the development of chronic inflammation are signature processes in HIV pathogenesis that propel progression to AIDS. Our recent ex vivo studies have revealed how most lymphoid CD4 T cells die by caspase-1-mediated-pyroptosis, an intensely inflammatory form of programmed cell death, providing an unexpected association between these two disease-promoting processes.

Progressive depletion of CD4 T cells is a hallmark of untreated acquired immune deficiency syndrome (AIDS), but the mechanism of CD4 T-cell death by HIV remains poorly understood. While HIV directly infects and kills CD4 T cells, the number of productively infected cells in vivo cannot account for the massive CD4 T-cell losses that occur. To better understand how HIV infection depletes CD4 T cells, we used primary human lymphoid aggregate cultures (HLAC) from human tonsil and spleen tissue. Using this system three surprising discoveries emerged.

The depletion of CD4 T cells and the development of chronic inflammation are signature processes in HIV pathogenesis that propel progression to AIDS. Our recent ex vivo studies have revealed how most lymphoid CD4 T cells die by caspase-1-mediated-pyroptosis, an intensely inflammatory form of programmed cell death, providing an unexpected association between these two disease-promoting processes.

Progressive depletion of CD4 T cells is a hallmark of untreated acquired immune deficiency syndrome (AIDS), but the mechanism of CD4 T-cell death by HIV remains poorly understood. While HIV directly infects and kills CD4 T cells, the number of productively infected cells in vivo cannot account for the massive CD4 T-cell losses that occur. To better understand how HIV infection depletes CD4 T cells, we used primary human lymphoid aggregate cultures (HLAC) from human tonsil and spleen tissue. Using this system three surprising discoveries emerged.

The depletion of CD4 T cells and development of chronic inflammation represent signature pathological processes centrally contributing to clinical progression of HIV disease. Current therapy chiefly diminishes viral replication. Novel therapeutics preventing CD4 T-cell depletion and/or reducing chronic inflammation could form valuable adjuncts to antiviral medications potentially improving long-term clinical outcomes including limiting the early appearance of diseases associated with aging. Our studies suggest that these signature processes are, in fact, interrelated.