title: Immobilization of glycosylphosphatidylinositol-anchored proteins inhibits T cell growth but not function.
abstract: 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 beta and gamma 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-2Ralpha, beta and gamma 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.
authors.affiliation: Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Centre, The Toronto Hospital, Toronto, Ontario M5G 2M9, Canada.
authors.forename: M D
authors.initials: MD
authors.lastname: Marmor
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: T R
authors.initials: TR
authors.lastname: Malek
authors.forename: M
authors.initials: M
authors.lastname: Julius
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D000071178:CD48 Antigen; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D017261:Glycosylphosphatidylinositols / Q000037:antagonists & inhibitors / Q000502:physiology*; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000502:physiology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D018800:Thy-1 Antigens / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000950:Antigens, Ly; D000071178:CD48 Antigen; D002352:Carrier Proteins; C000604066:Cd48 protein, mouse; D017261:Glycosylphosphatidylinositols; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D018800:Thy-1 Antigens; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; C507935:Jak3 protein, mouse; D053613:Janus Kinase 1; D053616:Janus Kinase 3