Type I interferon-mediated stimulation of T cells by CpG DNA

Abstract

Immunostimulatory DNA and oligodeoxynucleotides containing unmethylated CpG motifs (CpG DNA) are strongly stimulatory for B cells and antigen- presenting cells (APCs). We report here that, as manifested by CD69 and B7-2 upregulation, CpG DNA also induces partial activation of T cells, including naive-phenotype T cells, both in vivo and in vitro. Under in vitro conditions, CpG DNA caused activation oft cells in spleen cell suspensions but failed to stimulate highly purified T cells unless these cells were supplemented with APCs. Three lines of evidence suggested that APC-dependent stimulation of T cells by CpG DNA was mediated by type I interferons (IFN- I). First, T cell activation by CpG DNA was undetectable in IFN-IR(-/-) mice. Second, in contrast to normal T cells, the failure of purified IFN-IR(-/-) T cells to respond to CpG DNA could not be overcome by adding normal IFN-IR+ APCs. Third, IFN-I (but not IFN-γ) caused the same pattern of partial T cell activation as CpG DNA. Significantly, T cell activation by IFN-I was APC independent. Thus, CpG DNA appeared to stimulate T cells by inducing APCs to synthesize IFN-I, which then acted directly on T cells via IFN-IR. Functional studies suggested that activation oft cells by IFN-I was inhibitory. Thus, exposing normal (but not IFN-IR(-/-)) T cells to CpG DNA in vivo led to reduced T proliferative responses after TCR ligation in vitro.