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J. Exp. Med.,
Volume 188, Number 12, December 21, 1998 2335-2342
By
From the * Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California
92037; 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 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
/ 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.
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