CpG-oligodeoxynucleotides co-stimulate primary T cells in the absence of antigen-presenting cells.
CpG-containing oligodeoxynucleotides (CpG-ODN) act as powerful adjuvant during in vivo induction of T cell responses. While CpG-ODN directly activate antigen-presenting cells (APC) and thus exert an extrinsic activity on T cells, it is unclear whether they directly affect T cells (intrinsic activity). Here we analyze the effects of CpG-ODN on T cells in an APC-free cell culture. We report that CpG-ODN co-stimulate T cells provided they were triggered via their TCR. CpG-ODN induced IL-2 production, IL-2 receptor expression and thus proliferation. Proliferation was blocked by cyclosporin A or anti-IL-2 monoclonal antibodies (mAb) but not by anti-IL-4 mAb. Moreover, CpG-co-stimulated T cells differentiated into cytolytic T lymphocytes in vitro. Of note, IL-2-driven growth of primed T cells was not affected by CpG-ODN. Co-stimulation was also operative in T cells from CD28-/- mice and in TCR-transgenic T cells stimulated with peptide. CpG-ODN-mediated co-stimulation of T cells in vitro may thus explain part of the potent adjuvant effects of CpG-ODN in vivo.
Bendigs
S
S
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität, München, Germany.
Salzer
U
U
Lipford
G B
GB
Wagner
H
H
Heeg
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D018106:CD28 Antigens; D016572:Cyclosporine; D015226:Dinucleoside Phosphates; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell; C015772:CpG dinucleotide