Abstract
Bacterial DNA and synthetic cytidine-phosphate-guanosine- oligodeoxynucleotides (CpG ODN) potently activate dendritic cells (DC) and therefore have been proposed as adjuvants for vaccination strategies. Although CpG ODN are considered as safe adjuvants this study shows that CpG ODN are responsible for enhanced antigen-specific skin inflammatory reactions. We used the murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in which hapten-specific CD8+ T cytotoxic 1 cells are effector cells. Subcutaneous injection of CpG ODN, 1 d before sensitization enhanced the CHS response to DNFB and resulted in increased recruitment of CD8+ T cells at the challenge sites, whereas control ODH injection did not have any effect. This effect was local and not systemic as it was only observed when DNFB was applied at the same site as the CpG motifs. CpG ODN-induced enhancement of CHS was due to increased antigen-presenting cell functions of DC since: (i) CpG ODN-injected skin revealed upregulated expression of major histocompatibility complex class II, CD80, and CD86 molecules and (ii) CpG ODN treatment of DNFB-derivatized DC enhanced the intensity of CHS responses after in vivo transfer. Taken together, the results show that CpG ODN may be responsible for immune side-effects such as worsening of T cell-mediated skin diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 488-493 |
| Number of pages | 6 |
| Journal | Journal of Investigative Dermatology |
| Volume | 123 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2004 |
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Keywords
- Allergic contact
- Antigens
- Dermatitis
- Immunotherapy
- Mice
ASJC Scopus subject areas
- Dermatology
Cite this
CpG immunostimulatory sequences enhance contact hypersensitivity responses in mice. / Akiba, Hitoshi; Satoh, Masataka; Iwatsuki, Keiji; Kaiserlian, Dominique; Nicolas, Jean François; Kaneko, Fumio.
In: Journal of Investigative Dermatology, Vol. 123, No. 3, 09.2004, p. 488-493.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CpG immunostimulatory sequences enhance contact hypersensitivity responses in mice
AU - Akiba, Hitoshi
AU - Satoh, Masataka
AU - Iwatsuki, Keiji
AU - Kaiserlian, Dominique
AU - Nicolas, Jean François
AU - Kaneko, Fumio
PY - 2004/9
Y1 - 2004/9
N2 - Bacterial DNA and synthetic cytidine-phosphate-guanosine- oligodeoxynucleotides (CpG ODN) potently activate dendritic cells (DC) and therefore have been proposed as adjuvants for vaccination strategies. Although CpG ODN are considered as safe adjuvants this study shows that CpG ODN are responsible for enhanced antigen-specific skin inflammatory reactions. We used the murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in which hapten-specific CD8+ T cytotoxic 1 cells are effector cells. Subcutaneous injection of CpG ODN, 1 d before sensitization enhanced the CHS response to DNFB and resulted in increased recruitment of CD8+ T cells at the challenge sites, whereas control ODH injection did not have any effect. This effect was local and not systemic as it was only observed when DNFB was applied at the same site as the CpG motifs. CpG ODN-induced enhancement of CHS was due to increased antigen-presenting cell functions of DC since: (i) CpG ODN-injected skin revealed upregulated expression of major histocompatibility complex class II, CD80, and CD86 molecules and (ii) CpG ODN treatment of DNFB-derivatized DC enhanced the intensity of CHS responses after in vivo transfer. Taken together, the results show that CpG ODN may be responsible for immune side-effects such as worsening of T cell-mediated skin diseases.
AB - Bacterial DNA and synthetic cytidine-phosphate-guanosine- oligodeoxynucleotides (CpG ODN) potently activate dendritic cells (DC) and therefore have been proposed as adjuvants for vaccination strategies. Although CpG ODN are considered as safe adjuvants this study shows that CpG ODN are responsible for enhanced antigen-specific skin inflammatory reactions. We used the murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in which hapten-specific CD8+ T cytotoxic 1 cells are effector cells. Subcutaneous injection of CpG ODN, 1 d before sensitization enhanced the CHS response to DNFB and resulted in increased recruitment of CD8+ T cells at the challenge sites, whereas control ODH injection did not have any effect. This effect was local and not systemic as it was only observed when DNFB was applied at the same site as the CpG motifs. CpG ODN-induced enhancement of CHS was due to increased antigen-presenting cell functions of DC since: (i) CpG ODN-injected skin revealed upregulated expression of major histocompatibility complex class II, CD80, and CD86 molecules and (ii) CpG ODN treatment of DNFB-derivatized DC enhanced the intensity of CHS responses after in vivo transfer. Taken together, the results show that CpG ODN may be responsible for immune side-effects such as worsening of T cell-mediated skin diseases.
KW - Allergic contact
KW - Antigens
KW - Dermatitis
KW - Immunotherapy
KW - Mice
UR - http://www.scopus.com/inward/record.url?scp=4143093876&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4143093876&partnerID=8YFLogxK
U2 - 10.1111/j.0022-202X.2004.23318.x
DO - 10.1111/j.0022-202X.2004.23318.x
M3 - Article
C2 - 15304088
AN - SCOPUS:4143093876
VL - 123
SP - 488
EP - 493
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 3
ER -