The pivotal role of dendritic cells in feline immunodeficiency virus infection

Abstract

Feline immunodeficiency virus (FIV) is the feline counterpart to human immunodeficiency virus. Dendritic cells (DC) are one of the first cell types encountered during lentivirus infections. The studies set forth in this dissertation initiated investigations into the interactions of FIV and DC. Accordingly, objectives addressed here were: (1) to develop methods to culture feline DC; (2) to evaluate the susceptibility of feline DC to FIV infection and determine whether virus is transferred to CD4+ T cells; and (3) to assess the feasibility of prophylactic autologous DC/inactivated FIV vaccination. Feline dendritic cells were cultured from blood-derived monocytes. Cell surface markers of feline DC were identified and compared with those of other species and contrasted with those of feline macrophages (MØ) to establish that the cells cultured were DC. This work established the system for subsequent FIV/DC interaction studies. DC proved to be minimally susceptible to FIV infection. Nevertheless, the virus-exposed DC were able to transfer infection effectively to autologous CD4+ T cells. Transfer of infection was evident whether CD4+ T cells were added to FIV-exposed and washed DC immediately or after DC were re-cultured for two days to allow for degradation of captured and unbound inoculum virus. While resting CD4+ T cell-DC co-cultures supported low level replication, replication in activated CD4+ T cell-DC co-cultures was robust. Thus, FIV has devised a facile means to establish infection through the inherent interaction of DC and T cells with antigens. Finally, an initial study was conducted to determine whether feline DC pulsed with chemically inactivated FIV plus synthetic cytosine-phosphate guanosine dinucleotides (CpG ODN) as adjuvant might induce protection against subsequent virulent FIV challenge. This autologous feline DC/FIV immunization did not protect recipient cats from FIV challenge. No differences were detected in FIV proviral loads, CD4+ T cell numbers, or anti-FIV humoral and cell-mediated immune responses between vaccinated vs. control animals, indicating a need for refinement of this vaccine strategy in future pursuits. The studies described here serve a basis for further work defining the role of dendritic cells in FIV infection and immunity.