| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 152, Issue 6 2753-2767, Copyright © 1994 by American Association of Immunologists
ARTICLES |
GR Majeau, W Meier, B Jimmo, D Kioussis and PS Hochman
Biogen Inc., Cambridge, MA 02142.
Soluble ligands specific for cell surface molecules involved in APC-T cell interactions can signal cells and modulate immune responses. Recently, we reported that LFA3TIP, a fusion protein comprised of the first LFA-3 extracellular domain fused to the hinge, CH2, and CH3 regions of a human IgG1 inhibits proliferation of human T cells in vitro. We report herein the cell-based mechanism(s) of LFA3TIP in inhibition by studying the effects of structurally altered LFA3-Ig fusion proteins on proliferation of human PBL in vitro and on responses of mice transgenic for human CD2. We show that LFA3TIP inhibition requires expression of both the LFA-3 and CH2 domains of the fusion protein that bind CD2 and Fc gamma RI or Fc gamma RIII, respectively. LFA3TIP forms an intracellular Fc gamma R/CD2 bridge and directs cytolysis of CD2+ cells by freshly drawn human PBL in vitro as well as the non-C-mediated depletion of peripheral T cells of human CD2 transgenic mice. The cell-based mechanism(s) of LFA3TIP inhibition are discussed.
This article has been cited by other articles:
|
|
 |
|
  M. L. Dustin, T. Starr, D. Coombs, G. R. Majeau, W. Meier, P. S. Hochman, A. Douglass, R. Vale, B. Goldstein, and A. Whitty Quantification and Modeling of Tripartite CD2-, CD58FC Chimera (Alefacept)-, and CD16-mediated Cell Adhesion J. Biol. Chem., November 30, 2007; 282(48): 34748 - 34757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Haider, M. A. Lowes, H. Gardner, R. Bandaru, K. Darabi, F. Chamian, T. Kikuchi, P. Gilleaudeau, M. S. Whalen, I. Cardinale, et al. Novel Insight into the Agonistic Mechanism of Alefacept In Vivo: Differentially Expressed Genes May Serve as Biomarkers of Response in Psoriasis Patients J. Immunol., June 1, 2007; 178(11): 7442 - 7449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Shoji-Hosaka, Y. Kobayashi, M. Wakitani, K. Uchida, R. Niwa, K. Nakamura, and K. Shitara Enhanced Fc-Dependent Cellular Cytotoxicity of Fc Fusion Proteins Derived from TNF Receptor II and LFA-3 by Fucose Removal from Asn-Linked Oligosaccharides J. Biochem., December 1, 2006; 140(6): 777 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Heffernan, M. Y. Hurley, K. S. Martin, D. I. Smith, and M. J. Anadkat Alefacept for Alopecia Areata Arch Dermatol, December 1, 2005; 141(12): 1513 - 1516. [Full Text] [PDF]
|
|
|
|
 |
|
 L S Winterfield, A Menter, K Gordon, and A Gottlieb Psoriasis treatment: current and emerging directed therapies Ann Rheum Dis, March 1, 2005; 64(suppl_2): ii87 - ii90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chamian, M. A. Lowes, S.-L. Lin, E. Lee, T. Kikuchi, P. Gilleaudeau, M. Sullivan-Whalen, I. Cardinale, A. Khatcherian, I. Novitskaya, et al. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris PNAS, February 8, 2005; 102(6): 2075 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Gordon, A. K. Vaishnaw, J. O'Gorman, J. Haney, and A. Menter Treatment of Psoriasis With Alefacept: Correlation of Clinical Improvement With Reductions of Memory T-Cell Counts Arch Dermatol, December 1, 2003; 139(12): 1563 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fava, E. Notidis, J. Hunt, V. Szanya, N. Ratcliffe, A. Ngam-ek, A. R. de Fougerolles, A. Sprague, and J. L. Browning A Role for the Lymphotoxin/LIGHT Axis in the Pathogenesis of Murine Collagen-Induced Arthritis J. Immunol., July 1, 2003; 171(1): 115 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lebwohl, E. Christophers, R. Langley, J. P. Ortonne, J. Roberts, and C. E. M. Griffiths An International, Randomized, Double-blind, Placebo-Controlled Phase 3 Trial of Intramuscular Alefacept in Patients With Chronic Plaque Psoriasis Arch Dermatol, June 1, 2003; 139(6): 719 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. da Silva, M. Brickelmaier, G. R. Majeau, Z. Li, L. Su, Y.-M. Hsu, and P. S. Hochman Alefacept, an Immunomodulatory Recombinant LFA-3/IgG1 Fusion Protein, Induces CD16 Signaling and CD2/CD16-Dependent Apoptosis of CD2+ Cells J. Immunol., May 1, 2002; 168(9): 4462 - 4471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Ellis, G. G. Krueger, and the Alefacept Clinical Study Group Treatment of Chronic Plaque Psoriasis by Selective Targeting of Memory Effector T Lymphocytes N. Engl. J. Med., July 26, 2001; 345(4): 248 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Thompson, P. Schneider, S. L. Kalled, L. Wang, E. A. Lefevre, T. G. Cachero, F. MacKay, S. A. Bixler, M. Zafari, Z.-Y. Liu, et al. BAFF Binds to the Tumor Necrosis Factor Receptor-like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population J. Exp. Med., July 3, 2000; 192(1): 129 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ettinger, J. L. Browning, S. A. Michie, W. van Ewijk, and H. O. McDevitt Disrupted splenic architecture, but normal lymph node development in mice expressing a soluble lymphotoxin-beta receptor-IgG1 fusion protein PNAS, November 12, 1996; 93(23): 13102 - 13107. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
