title: DC-HIL is a negative regulator of T lymphocyte activation.
abstract: T-cell activation is the net product of competing positive and negative signals transduced by regulatory molecules on antigen-presenting cells (APCs) binding to corresponding ligands on T cells. Having previously identified DC-HIL as a receptor expressed by APCs that contains an extracellular immunoglobulin (Ig)-like domain, we postulated that it plays a role in T-cell activation. To probe this function, we created soluble recombinant DC-HIL, which we observed to bind activated (but not resting) T cells, indicating that expression of the putative ligand on T cells is induced by activation. Binding of DC-HIL to naive T cells attenuated these cells' primary response to anti-CD3 antibody, curtailing IL-2 production, and preventing entry into the cell cycle. DC-HIL also inhibited reactivation of T cells previously activated by APCs (secondary response). By contrast, addition of soluble DC-HIL to either allogeneic or ovalbumin-specific lymphocyte reactions augmented T-cell proliferation, and its injection into mice during the elicitation (but not sensitization) phase of contact hypersensitivity exacerbated ear-swelling responses. Mutant analyses showed the inhibitory function of DC-HIL to reside in its extracellular Ig-like domain. We conclude that endogenous DC-HIL is a negative regulator of T lymphocyte activation, and that this native inhibitory function can be blocked by exogenous DC-HIL, leading to enhanced immune responses.
authors.affiliation: Department of Dermatology, The University of Texas Southwestern Medical Center and Dermatology Section, Medical Service, Dallas Veterans Affairs Medical Center, Dallas, TX, USA.
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Chung
authors.forename: Kota
authors.initials: K
authors.lastname: Sato
authors.forename: Irene I
authors.initials: II
authors.lastname: Dougherty
authors.forename: Ponciano D
authors.initials: PD
authors.lastname: Cruz
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ariizumi
mesh_terms: D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000276:immunology; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005136:Eye Proteins; D005260:Female; D008024:Ligands; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic