Dr. Love will use “single-cell immunology” technology to understand how certain cells help limit HIV infection from progressing to AIDS, a situation that occurs in a small percent of infected individuals who never develop the disease.
A small percentage of people infected with the HIV virus have not developed AIDS, even 15 years after infection. Immune responses in these “non-progressors,” as they are called, are thought to confer protections against the deleterious effects of the virus. Non-progressors are not limited to HIV infection; for instance, there are non-progressors among people infected with tuberculosis, Hepatitis C, and malaria. Studying how immune responses confer protection in non-progressors is hampered by difficulties in obtaining sufficient numbers of immune cells from patient samples, and especially in obtaining ample numbers of the highly specialized immune cells that attack the specific virus involved. New technologies have been recently developed, however, that can enable investigators simultaneously to analyze the functional, clinical, and genetic characteristics of individual immune cells.
Called “microengraving,” Dr. Love will apply these new technologies to studying individual immune cells in blood samples taken from people infected with the HIV virus. He will explore how immune responses limit the progression of viral replication in non-progressors but not in those whose infection has progressed to AIDS. He hypothesizes that there are distinct differences in populations of immune cells circulating in the bloodstream of HIV-infected progressors and non-progressors; and that differences occur both in responses by innate immune cells (dendritic cells and natural killer cells, which mount a generalized first line of defense) and by adaptive immune cells (specific T cells that mount a highly targeted attack of the HIV virus).
He will determine: (1) the breadth of the various immune substances, called cytokines, produced by T cells; (2) the genetic diversity among HIV-specific T cells that exhibit varied cytokine responses during different phases of HIV infection; and (3) the functions of innate immune cells that respond to the HIV virus to block the infection’s progression.