In vivo impact of CpG1826 oligodeoxynucleotide on CD8 T cell primary responses and survival

被引:21
作者
Beloeil, L
Tomkowiak, M
Angelov, G
Walzer, T
Dubois, P
Marvel, J
机构
[1] Inst Natl Sante & Rech Med, Equipe Immuno Apoptose, U503, Ctr Etude & Rech Virol & Immunol, F-69365 Lyon 07, France
[2] GlaxoSmithKline Biol, Rixensart, Belgium
关键词
D O I
10.4049/jimmunol.171.6.2995
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 [免疫学];
摘要
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-specitic 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. The Journal of Immunology, 2003.
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页码:2995 / 3002
页数:8
相关论文
共 53 条
[1]
Peptide antigen treatment of naive and virus-immune mice: Antigen-specific tolerance versus immunopathology [J].
Aichele, P ;
BrduschaRiem, K ;
Oehen, S ;
Odermatt, B ;
Zinkernagel, RM ;
Hengartner, H ;
Pircher, H .
IMMUNITY, 1997, 6 (05) :519-529
[2]
CpG DNA induces maturation of dendritic cells with distinct effects on nascent and recycling MHC-II antigen-processing mechanisms [J].
Askew, D ;
Chu, RS ;
Krieg, AM ;
Harding, CV .
JOURNAL OF IMMUNOLOGY, 2000, 165 (12) :6889-6895
[3]
Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs [J].
Ballas, ZK ;
Krieg, AM ;
Warren, T ;
Rasmussen, W ;
Davis, HL ;
Waldschmidt, M ;
Weiner, GJ .
JOURNAL OF IMMUNOLOGY, 2001, 167 (09) :4878-4886
[4]
Beckett S, 2002, CALL CENT MAG, V15, P8
[5]
The effects of DNA containing CpG motif on dendritic cells [J].
Behboudi, S ;
Chao, D ;
Klenerman, P ;
Austyn, J .
IMMUNOLOGY, 2000, 99 (03) :361-366
[6]
Help for cytotoxic-T-cell responses is mediated by CD40 signalling [J].
Bennett, SRM ;
Carbone, FR ;
Karamalis, F ;
Flavell, RA ;
Miller, JFAP ;
Heath, WR .
NATURE, 1998, 393 (6684) :478-480
[7]
CD28 COSTIMULATION CAN PROMOTE T-CELL SURVIVAL BY ENHANCING THE EXPRESSION OF BCL-X(L) [J].
BOISE, LH ;
MINN, AJ ;
NOEL, PJ ;
JUNE, CH ;
ACCAVITTI, MA ;
LINDSTEN, T ;
THOMPSON, CB .
IMMUNITY, 1995, 3 (01) :87-98
[8]
Enhanced dendritic cell maturation by TNF-α or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo [J].
Brunner, C ;
Seiderer, J ;
Schlamp, A ;
Bidlingmaier, M ;
Eigler, A ;
Haimerl, W ;
Lehr, HA ;
Krieg, AM ;
Hartmann, G ;
Endres, S .
JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6278-6286
[9]
Functional differences between memory and naive CD8 T cells [J].
Cho, BK ;
Wang, CY ;
Sugawa, S ;
Eisen, HN ;
Chen, JZ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :2976-2981
[10]
IFN-αβ promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines [J].
Cho, HJ ;
Hayashi, T ;
Datta, SK ;
Takabayashi, K ;
Van Uden, JH ;
Horner, A ;
Corr, M ;
Raz, E .
JOURNAL OF IMMUNOLOGY, 2002, 168 (10) :4907-4913