Timothy Lahey, MD
Regulatory T cells in HIV infection
The HIV epidemic remains a worldwide health crisis despite the introduction of antiretroviral therapy more than ten years ago. One hallmark characteristic of HIV disease is weakened HIV-specific cellular immune responses that fail to clear HIV viremia or prevent progression to AIDS. A recently characterized population of T cells called regulatory T cells may exacerbate this problem by suppressing HIV-specific effector T cell proliferation and cytokine secretion. However, the mechanisms through which regulatory T cells suppress HIV-specific cellular immune responses is unclear. The laboratory of Timothy Lahey MD is investigating the hypothesis that regulatory T cells suppress HIV-specific cellular immune responses through costimulatory pathways involving CD154 and CTLA-4. In addition, we are evaluating the impact of regulatory T cell interactions with effector T cells on the susceptibility of effector T cells to direct HIV infection, and resultant cell death. In so doing, we hope not only to uncover the mechanisms through which regulatory T cells undermine the immune response to HIV, but also to identify new therapies that might improve the immune response to HIV by interfering with regulatory T cell function.
Alix Howell, PhD
HIV in the Female Reproductive Tract
Research in the laboratory of Alexandra L. Howell, Ph.D. focuses on determining the mechanism by which HIV-1 infects cells and tissues within the female reproductive tract (FRT). Women are most commonly infected following heterosexual transmission of the virus, and determining the cell populations and mode of transmission of the virus to cells in the periphery could lead to the development of therapeutic approaches to preventing infection in women. Our studies involve the infection of primary cultures of both epithelial and stromal cells from FRT tissues that are obtained from women undergoing hysterectomy who consent to provide tissues for research. We infect the cells in vitro, using various strains of HIV-1 in order to understand the types of viral strains that initiate infection, and how mixtures of different viruses are preferentially replicated within the FRT. Our current studies focus on the role of the sex hormones estradiol and progesterone on infectivity, and we have shown that certain levels of these hormones can reduce viral replication in peripheral blood cells. These findings suggest that sex hormones may be used to reduce a woman's risk of acquiring HIV-1 infection after exposure to the virus.