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The R.W. Johnson Pharmaceutical Research Institute, San Diego, California 92121; and The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, RG20 7NN, United Kingdom
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 of T 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-
) 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 of T 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.
Key Words: type I interferons • CpG DNA • T cell stimulation • adjuvant • antigen-presenting cell stimulation
Abbreviations used: ICAM, intercellular adhesion molecule; KO, knockout; ODNs, oligodeoxynucleotides.
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