Type I interferon-mediated stimulation of T cells by CpG DNA.
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.
Sun
S
S
The R.W. Johnson Pharmaceutical Research Institute, San Diego, California 92121, USA.
Zhang
X
X
Tough
D F
DF
Sprent
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018899:CpG Islands; D004247:DNA / Q000494:pharmacology*; D004331:Drosophila melanogaster; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D017471:Receptors, Interferon / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051940:B7-2 Antigen; D004247:DNA; D006649:Histocompatibility Antigens; D007370:Interferon Type I; D007371:Interferon-gamma; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D017471:Receptors, Interferon; D000099192:CD69 Antigens; C497965:Cd86 protein, mouse