title: Costimulation through NKG2D enhances murine CD8+ CTL function: similarities and differences between NKG2D and CD28 costimulation.
abstract: Multiple studies have demonstrated that the NK cell activating receptor NKG2D can function as a costimulatory receptor for both mouse and human CD8+ T cells. However, it has recently been suggested that stimulation through NKG2D is insufficient for costimulation of CD8+ T cells. To aid in the delineation of NKG2D function in CTL responses, we investigated whether stimulation of NKG2D by the natural ligand RAE1epsilon was able to costimulate effector functions of a murine CTL line generated from DUC18 TCR transgenic mice. We found that NKG2D was able to costimulate DUC CTL responses and did so in a manner similar to CD28 costimulation. The T cells exhibited increased proliferation, IFN-gamma release, and cytotoxicity when presented antigenic peptide by P815 cells expressing RAE1epsilon or B7-1 compared with untransfected P815. In addition, both RAE1epsilon and B7-1 enhanced Ag-independent IFN-gamma secretion in response to IL-12 and IL-18 by DUC CTL. However, only costimulation through CD28 allowed for DUC CTL survival upon secondary stimulation, whereas ligation of NKG2D, but not CD28, induced DUC CTL to form an immune synapse with target cells in the absence of TCR stimulation. Understanding the outcomes of these differences may allow for a better understanding of T cell costimulation in general.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Markiewicz
authors.forename: Leonidas N
authors.initials: LN
authors.lastname: Carayannopoulos
authors.forename: Olga V
authors.initials: OV
authors.lastname: Naidenko
authors.forename: Ken
authors.initials: K
authors.lastname: Matsui
authors.forename: W Richard
authors.initials: WR
authors.lastname: Burack
authors.forename: Erica L
authors.initials: EL
authors.lastname: Wise
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins / Q000502:physiology; D029543:Nucleocytoplasmic Transport Proteins / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D055607:Receptors, Natural Killer Cell; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
chemical_list: D018122:B7-1 Antigen; D018106:CD28 Antigens; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma