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Distinct CpG oligonucleotide sequences activate human gamma delta T cells via interferon-alpha/-beta
S Rothenfusser1, V Hornung, A Krug
1Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Munich, Germany.
European Journal of Immunology
|December 18, 2001
Summary
Specific CpG oligodeoxynucleotides (ODN) activate natural killer (NK) and gamma delta T cells by inducing interferon-alpha/-beta. These CpG ODN act as potent immune adjuvants, enhancing responses to specific antigens.
Area of Science:
- Immunology
- Innate Immunity
- Adaptive Immunity
Background:
- Oligodeoxynucleotides with CpG motifs (CpG ODN) mimic microbial DNA and activate innate immunity effectors like NK cells.
- Human gamma delta T cells (Vgamma9/Vdelta2) are antigen-specific natural memory T cells that respond to non-protein phosphoantigens.
Purpose of the Study:
- To identify CpG ODN sequences that effectively activate gamma delta T cells and NK cells.
- To investigate the mechanism of CpG ODN-mediated activation of these immune cells.
- To evaluate the adjuvant potential of identified CpG ODN sequences.
Main Methods:
- Screening of various CpG ODN sequences for their ability to induce cytokine production (IFN-alpha/-beta) in peripheral blood mononuclear cells (PBMC).
- Assessing gamma delta T cell and NK cell activation through markers like CD69 expression, IFN-gamma production, perforin content, and lytic activity.
- Testing the synergistic effects of CpG ODN with cell-type-specific antigens.
- Investigating the role of cytokines (IFN-alpha/-beta) in CpG ODN-induced immune cell activation.
Main Results:
- Distinct CpG ODN sequences that induce high levels of IFN-alpha/-beta in PBMC elicited strong gamma delta T cell and NK cell responses.
- CpG ODN activated gamma delta T cells and NK cells independently and synergistically enhanced responses to specific antigens.
- Activation of gamma delta T cells and NK cells was mediated by IFN-alpha/-beta released from CpG ODN-stimulated PBMC.
- Purified gamma delta T cells and NK cells did not respond to CpG ODN directly but responded to recombinant IFN-alpha/-beta.
Conclusions:
- Specific CpG ODN sequences that induce high IFN-alpha/-beta are potent adjuvants for natural memory cells, including gamma delta T cells.
- Early IFN-alpha/-beta-dependent stimulation of IFN-gamma in NK and gamma delta T cells may contribute to a Th1 bias in immune responses.
- CpG ODN-induced cytokine production is crucial for activating gamma delta T cells and NK cells, highlighting their potential in immunotherapy.