ID: 34: Modulation of retrovirus-specific T cell responses by IFNα subtypes

Abstract

The expression of type I interferons (IFN) is the immediate host response during most viral infections. These cytokines induce an antiviral state in cells by the production of antiviral proteins, they can also modulate immune cell functions and elicit antiproliferative responses. IFN α belongs to a multigene family consisting of multiple IFN α subtypes (up to 14 in mice), and although they all bind the same receptor, they differ in their biological activities. We are interested in the immunoregulatory functions of different IFN α subtypes on virus-specific T cell responses during an acute Friend Retrovirus infection of mice. For analyzing CD4+ and CD8+ T cell proliferation, activation and effector functions we performed proliferation assays in vitro . We investigated a direct antiproliferative capacity of all tested IFN α subtypes – on both CD4+ and CD8+ T cell proliferation – with IFN α 9 having the strongest antiproliferative effect and IFN α 2 inhibiting cell proliferation the lowest. Additionally, IFN α 4 and IFN α 9 strongly induced the expression of cytokines like IL-2, TNF α , IFN γ or Granzyme B which depended on the presence of dendritic cells (DCs). To analyze virus-specific T cell responses in vivo , C57BL/6 mice were infected with Friend Virus and treated daily with different IFN α subtypes. Therapeutic treatment with IFN α 1, IFN α 4 and IFN α 11 significantly decreased viral loads during acute infection and prevented the expansion of CD4+, CD8+ and regulatory T cells in the bone marrow of infected mice. These results demonstrate the distinct immunostimulatory properties of IFN α subtypes which can be used to develop future immunotherapies against retroviruses.