Intercellular adhesion molecule-1 is necessary but not sufficient to activate CD4+ T cells. Discovery of a novel costimulator on kidney tubule cells.
Kidney tubule cells (KTC) are targets of T lymphocyte injury during allograft rejection and interstitial nephritis. KTC process and present self- and foreign Ags for immune recognition by CD4+ T cells in vivo and in vitro. However, it is not known whether KTC can provide the costimulatory signal required to fully activate CD4+ T cells. Using the MRL/MpJ fas<lpr> model of lupus interstitial nephritis, we found that KTC did not express the costimulators B7-1 or B7-2. Nevertheless, KTC from both normal and systemically infected mice provided non-B7 costimulation to splenic CD4+ T cells. T cell proliferation was blocked by mAbs binding intercellular adhesion molecule-1 (ICAM-1) but not by mAb or fusion proteins binding B7-1, B7-2, heat-stable Ag, or vascular cell adhesion molecule-1. Importantly, ICAM-1 expression was necessary but not sufficient to provide costimulation. The transformed KTC line D3.B7- expressed high levels of ICAM-1 but did not provide costimulation. Interestingly, KTC provided costimulation to splenic T cells but not to a Th1 clone. These results show that freshly isolated KTC can provide non-B7 costimulation to splenic T cells via an unidentified costimulator and ICAM-1. Furthermore, these experiments demonstrate the complex nature of T cell activation and show that at least for splenic T cells, three or more signals may be required for full activation on live APC.
Hagerty
D T
DT
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007684:Kidney Tubules / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000209:etiology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1