Serial intravascular staining reveals altered T cell trafficking in aged and SIV⁺ rhesus macaques

Abstract Lymphocyte trafficking is required for lymphocyte development and maturation, immune surveillance and response, and for immunological memory. While trafficking is integral for a functional immune system, it may also play a role in immune dysfunction. Patients with HIV and the elderly have immune dysfunction characterized by increased inflammation, immune activation, and susceptibility to infections and cancer. As trafficking is implicated in these processes, we hypothesized that these cohorts may have altered trafficking kinetics, resulting in immunosenescence. To determine the relationship between trafficking kinetics and immune dysfunction, we performed serial intravascular staining (SIVS) in healthy, aged, and SIV-infected rhesus macaques. SIVS uses sequential infusions of fluorescent antibody to label cells in vivo, enabling us to follow them as they migrate over time. In all animals, we found that naïve and central memory T cells underwent more and faster trafficking into tissues while effector memory and terminal effector T cells were more likely to remain in circulation. In SIV +and aged animals, we observed increased trafficking of all subsets into tissues. A possible result of increased trafficking is that naïve and central memory cells may spend less time in lymphoid tissue and may therefore be less likely to initiate an immune response. Increased trafficking of effector cells may result in cytotoxic cells entering tissues and potentially increasing inflammation, a hallmark of the immunosenesence found in both aged and HIV +patients. Using SIVS to evaluate trafficking in aged and SIV +rhesus provides new insights into the crucial role of lymphocyte trafficking in the immune system. Supported by Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health