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Infection and Immunity, December 2008, p. 5817-5825, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00793-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Primary Activation of Antigen-Specific Naive CD4+ and CD8+ T Cells following Intranasal Vaccination with Recombinant Bacteria{triangledown}

Annalisa Ciabattini,1 Elena Pettini,1 Peter Andersen,2 Gianni Pozzi,1 and Donata Medaglini1*

Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy,1 Department of Infectious Disease Immunity, Staten Serum Institute, Copenhagen, Denmark2

Received 25 June 2008/ Returned for modification 29 July 2008/ Accepted 29 September 2008

The primary activation of T-helper and T-cytotoxic cells following mucosal immunization with recombinant Streptococcus gordonii was studied in vivo by adoptive transfer of ovalbumin (OVA)-specific transgenic CD8+ (OT-I) and CD4+ (OT-II) T cells. A recombinant strain, expressing on the surface the vaccine antigen Ag85B-ESAT-6 from Mycobacterium tuberculosis fused to OVA T-helper and T-cytotoxic epitopes (peptides 323 to 339 and 257 to 264), was constructed and used to immunize C57BL/6 mice by the intranasal route. Recombinant, but not wild-type, bacteria induced OVA-specific CD4+ and CD8+ T-cell clonal expansion in cervical lymph nodes, lung, and spleen. OVA-specific CD4+ and CD8+ T-cell proliferation appeared first in cervical lymph nodes and later in the spleen, suggesting a possible migration of activated cells from the inductive site to the systemic district. A significant correlation between the percentages of CD4+ and CD8+ proliferating T cells was observed for each animal. The expression of CD69, CD44, and CD45RB on proliferating T lymphocytes changed as a function of the cell division number, confirming T-cell activation following the antigen encounter. These data indicate that intranasal immunization with recombinant S. gordonii is capable of inducing primary activation of naive antigen-specific CD4+ and CD8+ T cells, both locally and systemically.

* Corresponding author. Mailing address: LA. M. M. B., Università di Siena, Policlinico Le Scotte, V lotto piano 1, Viale Bracci, 53100 Siena, Italy. Phone: 39 577 233307. Fax: 39 577 233334. E-mail: medaglini{at}unisi.it

{triangledown} Published ahead of print on 6 October 2008.

Editor: A. Camilli

Infection and Immunity, December 2008, p. 5817-5825, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00793-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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