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Infection and Immunity, April 2003, p. 1740-1747, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1740-1747.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cholera Toxin and Its B Subunit Promote Dendritic Cell Vaccination with Different Influences on Th1 and Th2 Development

Kristina Eriksson,* Margareta Fredriksson, Inger Nordström, and Jan Holmgren

Department of Medical Microbiology & Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Göteborg, Sweden

Received 5 July 2002/ Returned for modification 24 October 2002/ Accepted 23 December 2002

Cholera toxin (CT) is a strong mucosal adjuvant for codelivered antigens, whereas its nontoxic B subunit (CTB) is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens. We investigated the effects of CT and CTB on the immunogenicity of in vitro-treated antigen-pulsed dendritic cells (DC) following intravenous injection into mice. Prior to infusion, DC were pulsed for 90 min with either free ovalbumin (OVA), OVA mixed with CT or CTB, or chemical conjugates of OVA with CT and CTB (OVA-CT and OVA-CTB). DC pulsed with OVA or with OVA and CTB gave rise to modest antibody and T-cell responses. Conjugation of OVA with CTB enhanced both the subsequent B-cell and T-cell responses to OVA and preferentially induced Th2 responses. CT was shown to be a strong adjuvant when it was coadministered to DC with OVA and was even stronger when it was coadministered with OVA-CTB and primed for a mixed Th1-Th2 response. The antibody and T-cell responses were further enhanced if OVA was coupled to CT, implying that CT can utilize a combined carrier and adjuvant function vis-a-vis linked antigens for DC vaccination. The immunopotentiating capacity of CT- and CTB-linked antigen was associated with both upregulated secretion of interleukin-1ß by the pulsed DC and increased expression of CD80 and CD86 on the DC surface. These results imply that CT and CTB can be used to both markedly increase and partially direct the DC vaccine-induced immune response with respect to Th1 and Th2 responses, which has obvious implications for DC-based vaccine development.


* Corresponding author. Mailing address: Department of Medical Microbiology & Immunology, Box 435, 405 30 Göteborg, Sweden. Phone: 46-31-3424761. Fax: 46-31-820160. E-mail: kristina.eriksson{at}microbio.gu.se.

Editor: V. J. DiRita


Infection and Immunity, April 2003, p. 1740-1747, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1740-1747.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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