In vivo impact of CpG1826 oligodeoxynucleotide on CD8 T cell primary responses and survival.
CpG oligodeoxynucleotide (ODN) promotes maturation of APCs in vivo and induces strong type 1 T cell responses in mice. In this study, we have investigated the ability of CpG1826 to modulate peptide-specific CD8 T cell responses in a context where CD4 T cells are likely to play a minor role. The effects of CpG1826 were evaluated in a system where a population of NP68-specific F5 TCR transgenic CD8 T cells is diluted into a polyclonal host following adoptive transfer into C57BL/10 syngeneic recipients. Using this approach, we found that CpG1826 enhanced the ability of F5 CD8 T cells to undergo multiple divisions in vivo, to express IFN-gamma ex vivo, and to up-regulate memory-associated cell surface markers such as CD122 (IL-2Rbeta) and Ly-6C. Moreover, CpG1826 greatly increased in vivo cytotoxic activity. Using tetramer detection, we found that CpG1826 promoted long-term survival of Ag-specific CD8 T cells after immunization while no NP68-specific cells were detected when the cognate peptide was injected alone. These results indicate that CpG1826 acts as an adjuvant which increases CD8 T cell effector responses and promotes long-term survival of NP68 peptide-specific cells in vivo. They also suggest that this adjuvant can modulate CD8 T cell responses in a system which is likely to be independent of CD4 T cell help.
Beloeil
Laurent
L
Centre d'Etude et de Recherche en Virologie et en Immunologie, Unité 503, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Lyon, France.
Tomkowiak
Martine
M
Angelov
Georgi
G
Walzer
Thierry
T
Dubois
Patrice
P
Marvel
Jacqueline
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D010455:Peptides / Q000494:pharmacology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000502:physiology
D000276:Adjuvants, Immunologic; D000950:Antigens, Ly; C423449:CpG ODN 1826; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D054353:Perforin; D004247:DNA