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* Laboratorio de Inmunología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile;
Millennium Nucleus on Immunology and Immunotherapy and Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile;
Millennium Nucleus on Immunology and Immunotherapy and Departamento de Ciencias, Fisiologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile;
Millennium Institute for Fundamental and Applied Biology and Fundacion Ciencia para la Vida, Santiago, Chile; and
¶ Universidad Andres Bello, Santiago, Chile
The acquired immune response begins with Ag presentation by dendritic cells (DCs) to naive T cells in a heterocellular cell-cell contact-dependent process. Although both DCs and T cells are known to express connexin43, a gap junction protein subunit, the role of connexin43 on the initiation of T cell responses remains to be elucidated. In the present work, we report the formation of gap junctions between DCs and T cells and their role on T cell activation during Ag presentation by DCs. In cocultures of DCs and T cells, Lucifer yellow microinjected into DCs is transferred to adjacent transgenic CD4+ T cells, only if the specific antigenic peptide was present at least during the first 24 h of cocultures. This dye transfer was sensitive to gap junction blockers, such as oleamide, and small peptides containing the extracellular loop sequences of conexin. Furthermore, in this system, gap junction blockers drastically reduced T cell activation as reflected by lower proliferation, CD69 expression, and IL-2 secretion. This lower T cell activation produced by gap junction blockers was not due to a lower expression of CD80, CD86, CD40, and MHC-II on DCs. Furthermore, gap junction blocker did not affect polyclonal activation of T cell induced with anti-CD3 plus anti-CD28 Abs in the absence of DCs. These results strongly suggest that functional gap junctions assemble at the interface between DCs and T cells during Ag presentation and that they play an essential role in T cell activation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Fondo Nacional de Ciencia y Tecnología 1070352 (to A.K.), 1070591 (to J.C.S.), 1060834 (to M.R.), and 1060253 (to M.R.B.), and grants DI 03-02 from Universidad Andrés Bello (to M.R.) and Núcleo Milenio P04/030-F (to A.K. and J.C.S.). R.E. was supported by Doctoral Fellowships from Programa de Mejoramiento de la Calidad y la Equidad de la Educación Superior and Consejo Nacional de Ciencia y Technología and from a grant from the Departamento de Postgrado and Postítulo, Universidad de Chile.
2 Current address: Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH 03756.
3 J.C.S. and M.R. contributed equally to this study.
4 Address correspondence and reprint requests to Dr. Juan C. Sáez, Departamento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile and Dr. Mario Rosemblatt, Fundación Ciencia para la Vida. Av. Zañartu 1482, Ñuñoa, Chile. E-mail addresses: jsaez{at}genes.bio.puc.cl or mrosembl{at}bionova.cl
5 Abbreviations used in this paper: DC, dendritic cell; Cx, connexin; Ly, Lucifer yellow; AGA, 18 
-glycyrrhetinic acid; BM-DC, bone marrow-derived dendritic cell; MHC II, MHC class II.
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