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) 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 Eisenbraun, M. D. Articles by Miller, R. A. Search for Related Content PubMed PubMed Citation Articles by Eisenbraun, M. D. Articles by Miller, R. A.

Altered Composition of the Immunological Synapse in an Anergic, Age-Dependent Memory T Cell Subset¹

Michael D. Eisenbraun^*,, Ami Tamir and Richard A. Miller^2,*,,,§

^* Cellular and Molecular Biology Graduate Program and Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and Institute of Gerontology and ^§ Geriatrics Center and Veterans Affairs Medical Center, Ann Arbor, MI 48109

In young mice, memory CD4 T lymphocytes with high P-glycoprotein activity (P-gp^high) are unresponsive to TCR stimulation in vitro but can be activated by PMA plus ionomycin. The proportion of these hyporesponsive cells increases considerably with age. The earliest events in T cell activation were studied in P-gp^high and P-gp^low CD4 memory cells at the single-cell level using confocal immunofluorescence methods. Recruitment of both linker for activation of T cells (LAT) and protein kinase C- to the immunological synapse, i.e., the site of T cell interaction with stimulator cells, was greatly impaired in P-gp^high cells from both young and old mice. Translocation of NF-AT to the nucleus, CD69 expression, and proliferative capacity were also diminished to a similar extent in P-gp^high cells under the same activation conditions. In contrast, movement of c-Cbl to the synapse region occurred in a high proportion of CD4 memory T cells regardless of P-gp subset or age. Moreover, although P-gp^low cells frequently recruited both c-Cbl and LAT to the APC synapse, cells in the less responsive P-gp^high subset frequently relocated c-Cbl, but not LAT, to the interface region. In some systems, c-Cbl can act as a negative regulator of receptor-dependent tyrosine kinases, and alterations of c-Cbl to LAT ratios in the P-gp^high subset may thus contribute to the hyporesponsiveness of this age-dependent, anergic memory cell population.

This article has been cited by other articles:

				H. Mattoo, M. Faulkner, U. Kandpal, R. Das, V. Lewis, A. George, S. Rath, J. M. Durdik, and V. Bal Naive CD4 T cells from aged mice show enhanced death upon primary activation Int. Immunol., November 1, 2009; 21(11): 1277 - 1289. [Abstract] [Full Text] [PDF]

				L. M. Carlin, K. Yanagi, A. Verhoef, E. N. M. N.-t Hoen, J. Yates, L. Gardner, J. Lamb, G. Lombardi, M. J. Dallman, and D. M. Davis Secretion of IFN-{gamma} and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse Blood, December 1, 2005; 106(12): 3874 - 3879. [Abstract] [Full Text] [PDF]

				N. N. Berg-Brown, M. A. Gronski, R. G. Jones, A. R. Elford, E. K. Deenick, B. Odermatt, D. R. Littman, and P. S. Ohashi PKC{theta} Signals Activation versus Tolerance In Vivo J. Exp. Med., March 15, 2004; 199(6): 743 - 752. [Abstract] [Full Text] [PDF]

				A. Ortiz-Suarez and R. A. Miller Antigen-Independent Expansion of CD28hi CD8 Cells From Aged Mice: Cytokine Requirements and Signal Transduction Pathways J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2003; 58(12): B1063 - 1073. [Abstract] [Full Text] [PDF]

				V. Jankovic, I. Messaoudi, and J. Nikolich-Zugich Phenotypic and functional T-cell aging in rhesus macaques (Macaca mulatta): differential behavior of CD4 and CD8 subsets Blood, November 1, 2003; 102(9): 3244 - 3251. [Abstract] [Full Text] [PDF]

				G. G. Garcia and R. A. Miller Age-Dependent Defects in TCR-Triggered Cytoskeletal Rearrangement in CD4+ T Cells J. Immunol., November 1, 2002; 169(9): 5021 - 5027. [Abstract] [Full Text] [PDF]

				M. S. Fassett, D. M. Davis, M. M. Valter, G. B. Cohen, and J. L. Strominger Signaling at the inhibitory natural killer cell immune synapse regulates lipid raft polarization but not class I MHC clustering PNAS, November 20, 2001; (2001) 211563598. [Abstract] [Full Text] [PDF]

				K. Flurkey, J. Papaconstantinou, R. A. Miller, and D. E. Harrison Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production PNAS, May 18, 2001; (2001) 111158898. [Abstract] [Full Text]

				G. G. Garcia and R. A. Miller Single-Cell Analyses Reveal Two Defects in Peptide-Specific Activation of Naive T Cells from Aged Mice J. Immunol., March 1, 2001; 166(5): 3151 - 3157. [Abstract] [Full Text] [PDF]

				K. H. Kirsch, M.-M. Georgescu, T. Shishido, W. Y. Langdon, R. B. Birge, and H. Hanafusa The Adapter Type Protein CMS/CD2AP Binds to the Proto-oncogenic Protein c-Cbl through a Tyrosine Phosphorylation-regulated Src Homology 3 Domain Interaction J. Biol. Chem., February 9, 2001; 276(7): 4957 - 4963. [Abstract] [Full Text] [PDF]

				K. Flurkey, J. Papaconstantinou, R. A. Miller, and D. E. Harrison Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production PNAS, June 5, 2001; 98(12): 6736 - 6741. [Abstract] [Full Text] [PDF]

				M. S. Fassett, D. M. Davis, M. M. Valter, G. B. Cohen, and J. L. Strominger Signaling at the inhibitory natural killer cell immune synapse regulates lipid raft polarization but not class I MHC clustering PNAS, December 4, 2001; 98(25): 14547 - 14552. [Abstract] [Full Text] [PDF]