Monocyte inflammatory protein-1α facilitates priming of CD8+ T cell responses to exogenous viral antigen

Abstract

Dendritic cells (DC) derived from bone marrow precursors of BALB/c or C57BL/6 mice in low-serum cultures supplemented with granulocyte macrophage colony stimulating factor and Flt3 ligand were pulsed in vitro with hepatitis B surface antigen (HBsAg) particles. DC processed exogenous HBsAg and presented its MHC class I-binding epitopes to cytotoxic T lymphocytes (CTL). This specific and restricted interaction of DC with CTL stimulated release of IFN-γ and macrophage inflammatory protein (MIP)-1α from the responding CTL. MIP-1α enhanced the survival of DC in vitro but did not induce proliferation. Furthermore, co-delivery of MIP-1α facilitated CTL priming in vivo to exogenous HBsAg in low responder C57BL/6 (H-2b) mice: a single injection of a low dose of HBsAg particles (without further adjuvants) successfully primed Kb-restricted CTL responses to HBsAg only when the exogenous antigen was co-delivered with 100 ng MIP-1α. These in vitro and in vivo data point to an important role of MIP-1α in the DC-dependent priming of CTL to exogenous viral antigens.