Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print December 12, 2007
Mol. Biol. Cell 10.1091/mbc.E07-07-0650

A more recent version of this article appeared on February 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-07-0650v1
19/2/701    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Olazabal, I. M.
Right arrow Articles by Sánchez-Madrid, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olazabal, I. M.
Right arrow Articles by Sánchez-Madrid, F.

Submitted on July 10, 2007
Revised on November 16, 2007
Accepted on November 28, 2007

Activation Outcomes Induced in Naïve CD8 T Cells by Macrophages Primed via "Phagocytic" and Non-"Phagocytic" Pathways

Isabel María Olazabal,* Noa Beatriz Martín-Cofreces,* María Mittelbrunn,{dagger} Gloria Martínez del Hoyo,{dagger} Balbino Alarcón,{ddagger} and Francisco Sánchez-Madrid*{dagger}

*Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; {dagger}Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; {ddagger}Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain

Monitoring Editor: J. Silvio Gutkind

The array of phagocytic receptors expressed by macrophages make them very efficient at pathogen clearance and the phagocytic process links innate with adaptive immunity. Primary macrophages modulate antigen cross-presentation and T-cell activation. We assessed ex vivo the putative role of different phagocytic receptors in immune synapse formation with CD8 naïve T-cells from OT-I transgenic mice, and compared this with the administration of antigen as a soluble peptide. Macrophages that have phagocytosed antigen induce T-cell MTOC and F-actin cytoskeleton relocalization to the contact site, as well as the recruitment of proximal TCR signals such as activated Vav1 and PKC [theta]. At the same doses of loaded antigen (1 µM), ‘phagocytic’ macrophages were more efficient than peptide-antigen loaded macrophages at forming productive immune synapses with T-cells, as indicated by active T-cell TCR/CD3 conformation, LAT phosphorylation, IL-2 production, and T-cell proliferation. Similar T-cell proliferation efficiency was obtained when low doses of soluble peptide (3–30 nM) were loaded on macrophages. These results suggest that the pathway used for antigen uptake may modulate the antigen density presented on MHC-I resulting in different signals induced in naïve CD8 T-cells, leading either to CD8 T-cell activation or anergy.

Address correspondence to: Francisco Sánchez-Madrid (fsanchez.hlpr{at}salud.madrid.org)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.