Immunology
Abstract
A pathogenic hallmark of rheumatoid arthritis (RA) is persistent activation of self-reactive CD4+ T cells. The cause of this aberrant activity remains elusive. We report here detection of autoantibodies against B7-H1, a recently described member of the B7 family, in 29% of patients with RA versus 4% of healthy donors. High-level expression of cell surface B7-H1 are found on activated human CD4+, CD8+, and CD45RO+ T cells. Immobilized autoantibodies to B7-H1 are capable of costimulating the proliferation of CD4+ T cells in vitro, and the presence of these autoantibodies correlates with active disease status. Using immobilized B7-H1 mAb’s and programmed death 1Ig, we demonstrate that engagement of B7-H1 on CD4+ T cells costimulates proliferation and secretion of IL-10, and subsequently leads to programmed cell death, accompanied with upregulated expression of TNF-related apoptosis–inducing ligand and activation of caspase-3. Taken together with our previous findings, these data indicate a bidirectional signaling role of B7-H1 in T cell costimulation and apoptosis and implicate B7-H1 autoantibodies as contributing to the progression of RA by inducing aberrant T cell responses.
Authors
Haidong Dong, Scott E. Strome, Eric L. Matteson, Kevin G. Moder, Dallas B. Flies, Gefeng Zhu, Hideto Tamura, Colin L.W. Driscoll, Lieping Chen
Abstract
We have previously described the identification of Artemis, a factor involved in the nonhomologous end joining (NHEJ) phase of V(D)J recombination of T and B cell receptor genes. Null mutations of the Artemis gene result in a complete absence of T and B lymphocytes that is associated with increased cell radiosensitivity, causing the radiosensitive T–B– SCID (RS-SCID) condition. We presently report the occurrence of hypomorphic mutations of the Artemis gene in four patients from two kindreds. Partially preserved in vivo activity of Artemis is associated with the presence of polyclonal T and B lymphocyte populations, albeit in reduced numbers, along with chromosomal instability and development of EBV-associated lymphoma in two of four patients. This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors.
Authors
Despina Moshous, Christophe Pannetier, Régina de Chasseval, Françoise le Deist, Marina Cavazzana-Calvo, Serge Romana, Elizabeth Macintyre, Danielle Canioni, Nicole Brousse, Alain Fischer, Jean-Laurent Casanova, Jean-Pierre de Villartay
Abstract
Research Article
Authors
Christian F. Krieglstein, Wolfgang H. Cerwinka, Andrew G. Sprague, F. Stephen Laroux, Matthew B. Grisham, Victor E. Koteliansky, Norbert Senninger, D. Neil Granger, Antonin R. de Fougerolles
Multiepitope CD8+ T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting
Abstract
Research Article
Authors
Valérie Dutoit, Robert N. Taub, Kyriakos P. Papadopoulos, Susan Talbot, Mary-Louise Keohan, Michelle Brehm, Sacha Gnjatic, Paul E. Harris, Brygida Bisikirska, Philippe Guillaume, Jean-Charles Cerottini, Charles S. Hesdorffer, Lloyd J. Old, Danila Valmori
Abstract
Research Article
Authors
Soon H. Kim, Mary M. Cleary, Howard S. Fox, David Chantry, Nora Sarvetnick
Abstract
Research Article
Authors
Kurt Redlich, Silvia Hayer, Romeo Ricci, Jean-Pierre David, Makiyeh Tohidast-Akrad, George Kollias, Günter Steiner, Josef S. Smolen, Erwin F. Wagner, Georg Schett
Abstract
Research Article
Authors
Karl-Johan Malmberg, Victor Levitsky, Håkan Norell, Cristina Teixeira de Matos, Mattias Carlsten, Kjell Schedvins, Hodjattallah Rabbani, Alessandro Moretta, Kalle Söderström, Jelena Levitskaya, Rolf Kiessling
Abstract
Research Article
Authors
Benjamin J. Staudinger, Michele A. Oberdoerster, Patrick J. Lewis, Henry Rosen
Abstract
Research Article
Authors
Lilin Wang, Dan Smith, Simona Bot, Luis Dellamary, Amy Bloom, Adrian Bot
Abstract
Research Article
Authors
Edwin Liu, Hiroaki Moriyama, Norio Abiru, Dongmei Miao, Liping Yu, Robert M. Taylor, Fred D. Finkelman, George S. Eisenbarth
Copyright © 2020 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)