HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barcia, C. Articles by Lowenstein, P. R. Search for Related Content PubMed PubMed Citation Articles by Barcia, C. Articles by Lowenstein, P. R. Pubmed/NCBI databases Substance via MeSH

In Vivo Polarization of IFN- at Kupfer and Non-Kupfer Immunological Synapses during the Clearance of Virally Infected Brain Cells^1,2

Carlos Barcia^*,, Kolja Wawrowsky^*,, Robert J. Barrett^*,, Chunyan Liu^*,, Maria G. Castro^*, and Pedro R. Lowenstein^3,*,

^* Board of Governors’ Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048; and Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095

Kupfer-type immunological synapses are thought to mediate intercellular communication between antiviral T cells and virally infected target Ag-presenting brain cells in vivo during an antiviral brain immune response. This hypothesis predicts that formation of Kupfer-type immunological synapses is necessary for polarized distribution of effector molecules, and their directed secretion toward the target cells. However, no studies have been published testing the hypothesis that cytokines can only form polarized clusters at Kupfer-type immunological synapses. Here, we show that IFN- and granzyme-B cluster in a polarized fashion at contacts between T cells and infected astrocytes in vivo. In some cases these clusters were found in Kupfer-type immunological synapses between T cells and infected astrocytes, but we also detected polarized IFN- at synaptic immunological contacts which did not form Kupfer-type immunological synaptic junctions, i.e., in the absence of polarization of TCR or LFA-1. This indicates that TCR signaling, which leads to the production, polarization, and eventual directed secretion of effector molecules such as IFN-, occurs following the formation of both Kupfer-type and non-Kupfer type immunological synaptic junctions between T cells and virally infected target astrocytes in vivo.

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 article is dedicated to the memory of Enrique C. Lowenstein (22 December 1914–18 April 2007). "Les vrais paradis sont les paradis qu’on a perdus." Marcel Proust

² This work is supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke Grant 1R01 NS44556.01, Minority Supplement NS445561.01, 1R21-NS054143.01, 1U01 NS052465.01, 1R03 TW006273-01 (to M.G.C.), National Institutes of Health/National Institute of Neurological Disorders and Stroke Grants 1R01 NS 054193.01; R01 NS 42893.01, U54 NS045309-01 and 1R21 NS047298-01 (to P.R.L.), The Bram and Elaine Goldsmith and the Medallions Group Endowed Chairs in Gene Therapeutics (to P.R.L. and M.G.C., respectively), The Linda Tallen and David Paul Kane Foundation Annual Fellowship, and the Board of Governors at Cedars-Sinai Medical Center.

C.B. performed the research, analyzed the data, and contributed to writing the paper, K.W. provided the 3-D reconstruction software and analyzed the data, R.B. analyzed the data and contributed to writing the paper, C.L. prepared the viral vectors, and M.G.C. and P.R.L. designed the research, analyzed the data, and wrote the paper.

³ Address correspondence and reprint requests to Dr. Pedro R. Lowenstein, Board of Governors’ Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 5090, Los Angeles, CA 90048. E-mail address: lowensteinp{at}cshs.org

⁴ Abbreviations used in this paper: SMAC, supramolecular activation clusters; c-SMAC, central supramolecular cluster; p-SMAC, peripheral supramolecular cluster; DAPI, 4',6-diamidino-2-phenylindole.

This article has been cited by other articles:

				C. Barcia Jr, A. Gomez, J. M. Gallego-Sanchez, A. Perez-Valles, M. G. Castro, P. R. Lowenstein, C. Barcia Sr, and M.-T. Herrero Infiltrating CTLs in Human Glioblastoma Establish Immunological Synapses with Tumorigenic Cells Am. J. Pathol., August 1, 2009; 175(2): 786 - 798. [Abstract] [Full Text] [PDF]

				C. Barcia, A. Gomez, V. de Pablos, E. Fernandez-Villalba, C. Liu, K. M. Kroeger, J. Martin, A. F. Barreiro, M. G. Castro, P. R. Lowenstein, et al. CD20, CD3, and CD40 Ligand Microclusters Segregate Three-Dimensionally In Vivo at B-Cell-T-Cell Immunological Synapses after Viral Immunity in Primate Brain J. Virol., October 15, 2008; 82(20): 9978 - 9993. [Abstract] [Full Text] [PDF]

				A. M. Beal, N. Anikeeva, R. Varma, T. O. Cameron, P. J. Norris, M. L. Dustin, and Y. Sykulev Protein Kinase C{theta} Regulates Stability of the Peripheral Adhesion Ring Junction and Contributes to the Sensitivity of Target Cell Lysis by CTL J. Immunol., October 1, 2008; 181(7): 4815 - 4824. [Abstract] [Full Text] [PDF]