Dendritic Cells Are Dispensable for T Cell Priming and Control of Acute Lymphocytic Choriomeningitis Virus Infection

Abstract

Dendritic cells (DCs) are considered to be the major APCs with potent activity for priming of naive CD4 and CD8 T cells. However, T cell priming can also be achieved by other APCs including macrophages, B cells, or even nonhematopoietic cell types. Systemic low-dose infection of mice with lymphocytic choriomeningitis virus (LCMV) results in massive expansion of virus-specific CD4 and CD8 T cells. To determine the role of DCs as APCs and source of type I IFNs in this infection model, we used ΔDC mice in which DCs are constitutively ablated because of expression of the diphtheria toxin α subunit within developing DCs. ΔDC mice showed lower serum concentrations of IFN-β and IL-12p40, but normal IFN-α levels during the first days postinfection. No differences were found for proliferation of transferred TCR-transgenic cells during the early phase of infection, suggesting that T cell priming occurred with the same efficiency in wild-type and ΔDC mice. Expansion and cytokine expression of endogenous LCMV-specific T cells was comparable between wild-type and ΔDC mice during primary infection and upon rechallenge of memory mice. In both strains of infected mice the viral load was reduced below the limit of detection with the same kinetic. Further, germinal center formation and LCMV-specific Ab responses were not impaired in ΔDC mice. This indicates that DCs are dispensable as APCs for protective immunity against LCMV infection.