The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1998/12/2335/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 12, December 21, 1998 2335-2342

Articles

Type I Interferon-mediated Stimulation of T Cells by CpG DNA

Siquan Sun{ddagger}, Xiaohong Zhang*, David F. Tough§, and Jonathan Sprent*

From the * Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California 92037; {ddagger} 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-{gamma}) 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

Address correspondence to Jonathan Sprent, Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 619-784-8619; Fax: 619-784-8839; E-mail: jsprent{at}scripps.edu

Abbreviations used: ICAM, intercellular adhesion molecule; KO, knockout; ODNs, oligodeoxynucleotides.


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