HIV-Specific T-cell Responses in Rectal Mucosa

Investigator: Peter Hunt, MD
Sponsor: University of California Davis

Location(s): United States


Most studies of antiviral immunity have focused on peripheral blood. However, the majority of lymphocytes are harbored in lymphoid tissues throughout the body. Mucosal lymphoid tissues serve as a portal of entry for HIV and as a site of active viral replication and CD4+ T-cell depletion. Therefore, studies of mucosal immunity are of particular importance for our understanding of HIV pathogenesis. Understanding the induction of antiviral immunity at mucosal surfaces is also of great relevance for vaccine development, as the majority of HIV transmission occurs through sexual contact.

We have established methods to detect antigen-specific T cells in mucosal tissues using clinical samples obtained by minimally invasive methods. We use a combination of approaches including flow cytometry, cellular immunology, and molecular biology, to study the trafficking patterns and effector functions of antigen-specific T cells. These translational research projects involve active collaborations with clinicians at UC Davis Medical Center and the University of California, San Francisco.

Key Questions to be addressed: 

• What are the effector functions of antiviral T-cells in mucosal tissues?

• What is the relationship between CD8+ T cell frequency and HIV viral load in tissues?

• What molecules (i.e., integrins, chemokines) are involved in the trafficking of antigen-specific T cells to mucosal tissues and to the central nervous system?

• How do immunization routes correlate with the induction of antiviral T cell responses in tissues?