International Immunology, Vol. 11, No. 9, 1381-1393,
September 1999
© 1999 Japanese Society for Immunology
Immobilization of glycosylphosphatidylinositol-anchored proteins inhibits T cell growth but not function
Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Centre, The Toronto Hospital, Toronto, Ontario M5G 2M9, Canada
1 Departments of Immunology and Medical Biophysics, University of Toronto and The Ontario Cancer Institute, The Toronto Hospital, Toronto, Ontario M5G 2M9, Canada
2 Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 31336, USA
Correspondence to: M. Julius, c/o 610 University Avenue, 620 University Avenue, Room 700B, Toronto, Ontario M5G 2M9, Canada
Accumulating evidence suggests that proteins tethered to the plasma membrane through glycosylphosphatidylinositol (GPI) anchors share common biological properties. In the present study we demonstrate that GPI-anchored proteins regulate T cell growth. Specifically, anti-TCR-induced proliferation was profoundly inhibited by co-immobilized mAb specific for Thy-1, CD48 and Ly6A/E. However, neither IL-2 production nor the effector function of cytotoxic T lymphocytes was impaired in these circumstances. Analysis of the IL-2 receptor (IL-2R) signaling pathway revealed that the association of IL-2R ß and 
chains with the Janus kinases, JAK1 and JAK3, was not perturbed in the presence of mAb specific for GPI-linked proteins. However, in these conditions,
IL-2-mediated recruitment of IL-2R
, ß and chains, resulting in the formation of the high-affinity hetero-trimeric IL-2R, was inhibited. The resulting phosphorylation of JAK1 and JAK3, indicative of their activation states, was correspondingly reduced. These results characterize a novel state of T cell physiology in which effector function is maintained, in the absence of clonal expansion. A physiological role for GPI-anchored proteins in the maintenance of cellular homeostasis and function is discussed.
Keywords: glycosylphosphatidylinositol-anchored proteins
3 Present address: Basel Institute for Immunology, Basel, CH 4005, Switzerland
Transmitting editor: J. F. Kearney
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Linden, V. R. Martins, M. A. M. Prado, M. Cammarota, I. Izquierdo, and R. R. Brentani Physiology of the Prion Protein Physiol Rev, April 1, 2008; 88(2): 673 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Gilner, W. G. Walton, K. Gush, and S. L. Kirby Antibodies to Stem Cell Marker Antigens Reduce Engraftment of Hematopoietic Stem Cells Stem Cells, February 1, 2007; 25(2): 279 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ballerini, P. Gourdain, V. Bachy, N. Blanchard, E. Levavasseur, S. Gregoire, P. Fontes, P. Aucouturier, C. Hivroz, and C. Carnaud Functional Implication of Cellular Prion Protein in Antigen-Driven Interactions between T Cells and Dendritic Cells. J. Immunol., June 15, 2006; 176(12): 7254 - 7262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. M. Haeryfar and D. W. Hoskin Thy-1: More than a Mouse Pan-T Cell Marker J. Immunol., September 15, 2004; 173(6): 3581 - 3588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. L. W. Hazenbos, Y. Murakami, J.-i. Nishimura, J. Takeda, and T. Kinoshita Enhanced Responses of Glycosylphosphatidylinositol Anchor-Deficient T Lymphocytes J. Immunol., September 15, 2004; 173(6): 3810 - 3815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Staffler, A. Szekeres, G. J. Schutz, M. D. Saemann, E. Prager, M. Zeyda, K. Drbal, G. J. Zlabinger, T. M. Stulnig, and H. Stockinger Selective Inhibition of T Cell Activation Via CD147 Through Novel Modulation of Lipid Rafts J. Immunol., August 15, 2003; 171(4): 1707 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y. Ito, C. Y. J. Li, A. Bernstein, J. E. Dick, and W. L. Stanford Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice Blood, January 15, 2003; 101(2): 517 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Goebel, K. Forrest, L. Morford, and T. L. Roszman Differential localization of IL-2- and -15 receptor chains in membrane rafts of human T cells J. Leukoc. Biol., July 1, 2002; 72(1): 199 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Klem, P. C. Verrett, V. Kumar, and J. D. Schatzle 2B4 Is Constitutively Associated with Linker for the Activation of T Cells in Glycolipid-Enriched Microdomains: Properties Required for 2B4 Lytic Function J. Immunol., July 1, 2002; 169(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Marmor and M. Julius Role for lipid rafts in regulating interleukin-2 receptor signaling Blood, September 1, 2001; 98(5): 1489 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vereb, J. Matko, G. Vamosi, S. M. Ibrahim, E. Magyar, S. Varga, A. Jenei, R. Gaspar Jr., T. A. Waldmann, and S. Damjanovich Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts PNAS, May 23, 2000; 97(11): 6013 - 6018. [Abstract] [Full Text] [PDF]
|
|