| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Amgen Institute, and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada; and
Department of Oral Biochemistry, Kanagawa Dental College, Kanagawa, Japan
IL-2-activated NK cells exhibit cytotoxic activity against a wide
variety of tumor cells in a non-MHC-restricted fashion and in the
absence of prior sensitization. The molecular mechanisms that regulate
the cytotoxicity and attachment of activated killer cells to tumor
target cells are not known. We provide genetic evidence in
CD44-/- and LFA-1-/- mice that the
cell adhesion receptors LFA-1 and CD44 regulate the cytotoxic activity
of IL-2-activated NK cells against a variety of different tumor cells.
This defect in cytotoxicity was significantly enhanced in mice that
carried a double mutation of both CD44 and LFA-1. In vitro
differentiation, TNF-
and IFN-
production, and expression of the
cytolytic effector molecules perforin and Fas-L were comparable among
IL-2-activated NK cells from LFA-1-/-,
CD44-/-, CD44-/-LFA-1-/-, and
control mice. However, CD44-/-, LFA-1-/-,
and CD44-/-LFA-1-/- IL-2-activated NK cells
showed impaired binding and conjugate formation with target cells. We
also show that hyaluronic acid is the principal ligand on tumor cells
for CD44-mediated cytotoxicity of IL-2-activated NK cells. These
results provide the first genetic evidence of the role of adhesion
receptors in IL-2-activated NK killing. These data also indicate that
distinct adhesion receptors cooperate to mediate binding between
effector and target cells required for the initiation of "natural"
cytotoxicity.
This article has been cited by other articles:
|
|
 |
|
  P. Banerjee, G. Feuer, and E. Barker Human T-Cell Leukemia Virus Type 1 (HTLV-1) p12I Down-Modulates ICAM-1 and -2 and Reduces Adherence of Natural Killer Cells, Thereby Protecting HTLV-1-Infected Primary CD4+ T Cells from Autologous Natural Killer Cell-Mediated Cytotoxicity despite the Reduction of Major Histocompatibility Complex Class I Molecules on Infected Cells J. Virol., September 15, 2007; 81(18): 9707 - 9717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Back, A. Chalifour, L. Scarpellino, and W. Held Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact PNAS, March 6, 2007; 104(10): 3978 - 3983. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. M. Nolte-'t Hoen, C. R. Almeida, N. R. Cohen, S. Nedvetzki, H. Yarwood, and D. M. Davis Increased surveillance of cells in mitosis by human NK cells suggests a novel strategy for limiting tumor growth and viral replication Blood, January 15, 2007; 109(2): 670 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Suck, D. R. Branch, P. Aravena, M. Mathieson, S. Helke, and A. Keating Constitutively polarized granules prime KHYG-1 NK cells Int. Immunol., September 1, 2006; 18(9): 1347 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Fostel, J. Dluzniewska, Y. Shimizu, B. J. Burbach, and E. J. Peterson ADAP is dispensable for NK cell development and function Int. Immunol., August 1, 2006; 18(8): 1305 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Guerau-de-Arellano, J. Alroy, D. Bullard, and B. T. Huber Aggravated Lyme Carditis in CD11a-/- and CD11c-/- Mice Infect. Immun., November 1, 2005; 73(11): 7637 - 7643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. T. Bryceson, M. E. March, D. F. Barber, H.-G. Ljunggren, and E. O. Long Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells J. Exp. Med., October 3, 2005; 202(7): 1001 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Barber, M. Faure, and E. O. Long LFA-1 Contributes an Early Signal for NK Cell Cytotoxicity J. Immunol., September 15, 2004; 173(6): 3653 - 3659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Stehling, V. Grau, and B. Steiniger Monocyte cytotoxicity during acute kidney graft rejection in rats Int. Immunol., January 1, 2004; 16(1): 101 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. McKallip, M. Fisher, Y. Do, A. K. Szakal, U. Gunthert, P. S. Nagarkatti, and M. Nagarkatti Targeted Deletion of CD44v7 Exon Leads to Decreased Endothelial Cell Injury but Not Tumor Cell Killing Mediated by Interleukin-2-activated Cytolytic Lymphocytes J. Biol. Chem., October 31, 2003; 278(44): 43818 - 43830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Emoto, M. Miyamoto, Y. Emoto, I. Yoshizawa, V. Brinkmann, N. van Rooijen, and S. H. E. Kaufmann Highly Biased Type 1 Immune Responses in Mice Deficient in LFA-1 in Listeria monocytogenes Infection Are Caused by Elevated IL-12 Production by Granulocytes J. Immunol., October 15, 2003; 171(8): 3970 - 3976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Riteau, D. F. Barber, and E. O. Long Vav1 Phosphorylation Is Induced by {beta}2 Integrin Engagement on Natural Killer Cells Upstream of Actin Cytoskeleton and Lipid Raft Reorganization J. Exp. Med., August 4, 2003; 198(3): 469 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhao, H. Ohdan, J. O. Manilay, and M. Sykes NK Cell Tolerance in Mixed Allogeneic Chimeras J. Immunol., June 1, 2003; 170(11): 5398 - 5405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shingu, C. Kruschinski, A. Luhrmann, K. Grote, T. Tschernig, S. von Horsten, and R. Pabst Intratracheal Macrophage-Activating Lipopeptide-2 Reduces Metastasis in the Rat Lung Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 316 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Matsumoto, S. Tsunematsu, K.-i. Tsukinoki, Y. Ohmi, M. Iwamiya, A. Oliveira-dos-Santos, D. Tone, J. Shindo, and J. M. Penninger Essential Role of the Adhesion Receptor LFA-1 for T Cell-Dependent Fulminant Hepatitis J. Immunol., December 15, 2002; 169(12): 7087 - 7096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Noutsias, M. Pauschinger, H.-P. Schultheiss, and U. Kuhl Advances in the immunohistological diagnosis of inflammatory cardiomyopathy Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I54 - I62. [Abstract] [PDF]
|
|
|
|
|
|
D. Bechard, A. Scherpereel, H. Hammad, T. Gentina, A. Tsicopoulos, M. Aumercier, J. Pestel, J.-P. Dessaint, A.-B. Tonnel, and P. Lassalle Human Endothelial-Cell Specific Molecule-1 Binds Directly to the Integrin CD11a/CD18 (LFA-1) and Blocks Binding to Intercellular Adhesion Molecule-1 J. Immunol., September 15, 2001; 167(6): 3099 - 3106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Foger, R Marhaba, and M Zoller Involvement of CD44 in cytoskeleton rearrangement and raft reorganization in T cells J. Cell Sci., January 3, 2001; 114(6): 1169 - 1178. [Abstract] [PDF]
|
|
|
|
|
|
T. Takahashi, M. Nieda, Y. Koezuka, A. Nicol, S. A. Porcelli, Y. Ishikawa, K. Tadokoro, H. Hirai, and T. Juji Analysis of Human V{alpha}24+ CD4+ NKT Cells Activated by {alpha}-Glycosylceramide-Pulsed Monocyte-Derived Dendritic Cells J. Immunol., May 1, 2000; 164(9): 4458 - 4464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Q. Rafi-Janajreh, D. Chen, R. Schmits, T. W. Mak, R. L. Grayson, D. P. Sponenberg, M. Nagarkatti, and P. S. Nagarkatti Evidence for the Involvement of CD44 in Endothelial Cell Injury and Induction of Vascular Leak Syndrome by IL-2 J. Immunol., August 1, 1999; 163(3): 1619 - 1627. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
