IAI Accepts, published online ahead of print on 6 October 2008

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Infect. Immun. doi:10.1128/IAI.00793-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Primary activation of antigen-specific naive CD4⁺ and CD8⁺ T cells following intranasal vaccination with recombinant bacteria

Annalisa Ciabattini, Elena Pettini, Peter Andersen, Gianni Pozzi, and Donata Medaglini^*

Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy; Department of Infectious Disease Immunity, Staten Serum Institute, Copenhagen, Denmark

^* To whom correspondence should be addressed. Email: medaglini{at}unisi.it.

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 (323-339 and 257-264), was constructed and used to immunize C57BL/6 mice by the intranasal route. Recombinant bacteria, but not wild type, 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 percentage of CD4⁺ and CD8⁺ proliferating T cells was observed in each animal. The expression of CD69, CD44 and CD45RB on proliferating T lymphocytes changed as a function of cell division number, confirming T-cell activation following antigen encounter. These data indicate that intranasal immunization with recombinat S. gordonii is capable of inducing primary activation of naive antigen-specific CD4⁺ and CD8⁺ T cells both locally and systemically.