Brain, Vol. 123, No. 6, 1092-1101,
June 2000
© 2000 Oxford University Press
Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment
1 Section of Immunobiology, 2 Howard Hughes Medical Institute and 3 Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA
Correspondence to:
Dr Michael D. Carrithers, Section of Immunobiology, Yale University School of Medicine, PO Box 208011, 310 Cedar Street, New Haven, CT 06520-8011, USA
Activated CD4 Th1 lymphocytes can enter the brain in the absence of an inflammatory focus. However, the molecular mediators that regulate this early migration of lymphocytes into the brain have remained unclear. We hypothesized that the entry of these `pioneer' lymphocytes into the brain is regulated by a set of molecular events that are distinct from those used once inflammation has been established. Using cells fluorescently labelled with the lipophilic dye DiI, myelin basic protein (MBP)-specific CD4 lymphocytes that expressed low or high levels of very late antigen-4 (VLA-4) and non-antigen-specific activated splenocytes homed to mouse brain in similar quantities 2 h after adoptive transfer. However, antigen specificity and VLA-4 expression were required for more robust recruitment by 24h. Immunocytochemistry revealed endothelial and microenvironmental upregulation of vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule 1 (ICAM-1), MHC class II and interferon-
48 h after transfer of MBP-specific cells. In contrast, expression of meningeal and choroid plexus-associated P selectin was upregulated 2 h after adoptive transfer, but not at 48 h. Monoclonal antibody to P selectin, but not to VLA-4, inhibited early migration of high VLA-4-expressing MBP-specific lymphocytes. These results suggest that early migration occurs independent of the lymphocyte integrin VLA-4 and endothelial VCAM, but does require increased surface expression of endothelial P selectin.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. R. Lees, Y. Iwakura, and J. H. Russell Host T Cells Are the Main Producers of IL-17 within the Central Nervous System during Initiation of Experimental Autoimmune Encephalomyelitis Induced by Adoptive Transfer of Th1 Cell Lines J. Immunol., June 15, 2008; 180(12): 8066 - 8072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Chen and T. D. Palmer Cellular repair of CNS disorders: an immunological perspective Hum. Mol. Genet., April 15, 2008; 17(R1): R84 - R92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Doring, M. Wild, D. Vestweber, U. Deutsch, and B. Engelhardt E- and P-Selectin Are Not Required for the Development of Experimental Autoimmune Encephalomyelitis in C57BL/6 and SJL Mice J. Immunol., December 15, 2007; 179(12): 8470 - 8479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Galea, M. Bernardes-Silva, P. A. Forse, N. van Rooijen, R. S. Liblau, and V. H. Perry An antigen-specific pathway for CD8 T cells across the blood-brain barrier J. Exp. Med., September 3, 2007; 204(9): 2023 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Bullard, X. Hu, T. R. Schoeb, R. G. Collins, A. L. Beaudet, and S. R. Barnum Intercellular Adhesion Molecule-1 Expression Is Required on Multiple Cell Types for the Development of Experimental Autoimmune Encephalomyelitis J. Immunol., January 15, 2007; 178(2): 851 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Kurschus, T. Oelert, B. Liliensiek, P. Buchmann, D. C. Wraith, G. J. Hammerling, and B. Arnold Experimental autoimmune encephalomyelitis in mice expressing the autoantigen MBP1-10 covalently bound to the MHC class II molecule I-Au Int. Immunol., January 1, 2006; 18(1): 151 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Piccio, B. Rossi, L. Colantonio, R. Grenningloh, A. Gho, L. Ottoboni, J. W. Homeister, E. Scarpini, M. Martinello, C. Laudanna, et al. Efficient Recruitment of Lymphocytes in Inflamed Brain Venules Requires Expression of Cutaneous Lymphocyte Antigen and Fucosyltransferase-VII J. Immunol., May 1, 2005; 174(9): 5805 - 5813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P.A. Rice, H.-P. Hartung, and P. A. Calabresi Anti-{alpha}4 integrin therapy for multiple sclerosis: Mechanisms and rationale Neurology, April 26, 2005; 64(8): 1336 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kerfoot, E. M. Long, M. J. Hickey, G. Andonegui, B. M. Lapointe, R. C. O. Zanardo, C. Bonder, W. G. James, S. M. Robbins, and P. Kubes TLR4 Contributes to Disease-Inducing Mechanisms Resulting in Central Nervous System Autoimmune Disease J. Immunol., December 1, 2004; 173(11): 7070 - 7077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ni, E. B Geller, M. J Eppihimer, T. K Eisenstein, M. W Adler, and R. F Tuma Win 55212-2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model Multiple Sclerosis, April 1, 2004; 10(2): 158 - 164. [Abstract] [PDF]
|
|
|
|
 |
|
 P. Kivisakk, D. J. Mahad, M. K. Callahan, C. Trebst, B. Tucky, T. Wei, L. Wu, E. S. Baekkevold, H. Lassmann, S. M. Staugaitis, et al. Human cerebrospinal fluid central memory CD4+ T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin PNAS, July 8, 2003; 100(14): 8389 - 8394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Battistini, L. Piccio, B. Rossi, S. Bach, S. Galgani, C. Gasperini, L. Ottoboni, D. Ciabini, M. D. Caramia, G. Bernardi, et al. CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1 Blood, June 15, 2003; 101(12): 4775 - 4782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Denkinger, M. Denkinger, J. J. Kort, C. Metz, and T. G. Forsthuber In Vivo Blockade of Macrophage Migration Inhibitory Factor Ameliorates Acute Experimental Autoimmune Encephalomyelitis by Impairing the Homing of Encephalitogenic T Cells to the Central Nervous System J. Immunol., February 1, 2003; 170(3): 1274 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Kwok, H. Miletic, S. Lutjen, S. Soltek, M. Deckert, and D. Schluter Protective Immunosurveillance of the Central Nervous System by Listeria-Specific CD4 and CD8 T Cells in Systemic Listeriosis in the Absence of Intracerebral Listeria J. Immunol., August 15, 2002; 169(4): 2010 - 2019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kerfoot and P. Kubes Overlapping Roles of P-Selectin and {alpha}4 Integrin to Recruit Leukocytes to the Central Nervous System in Experimental Autoimmune Encephalomyelitis J. Immunol., July 15, 2002; 169(2): 1000 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Issekutz and T. B. Issekutz The Role of E-Selectin, P-Selectin, and Very Late Activation Antigen-4 in T Lymphocyte Migration to Dermal Inflammation J. Immunol., February 15, 2002; 168(4): 1934 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Piccio, B. Rossi, E. Scarpini, C. Laudanna, C. Giagulli, A. C. Issekutz, D. Vestweber, E. C. Butcher, and G. Constantin Molecular Mechanisms Involved in Lymphocyte Recruitment in Inflamed Brain Microvessels: Critical Roles for P-Selectin Glycoprotein Ligand-1 and Heterotrimeric Gi-Linked Receptors J. Immunol., February 15, 2002; 168(4): 1940 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Hickey P selectin, pioneer cells and the path to inflammation Brain, June 1, 2000; 123(6): 1073 - 1074. [Full Text] [PDF]
|
|