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Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions

Authors
  • Tesselaar, Kiki1, 2
  • Arens, Ramon1, 2, 3
  • van Schijndel, Gijs M.W.2
  • Baars, Paul A.1, 2
  • van der Valk, Martin A.4
  • Borst, Jannie5
  • van Oers, Marinus H.J.3
  • van Lier, René A.W.1, 2
  • 1 Laboratory for Experimental Immunology, Academic Medical Center, P.O. Box 22700, Amsterdam, 1100DD, The Netherlands , Amsterdam (Netherlands)
  • 2 Sanquin/Research and Landsteiner Laboratory of the Academic Medical Center, Plesmanlaan 125, Amsterdam, 1066CX, The Netherlands , Amsterdam (Netherlands)
  • 3 Academic Medical Center, P.O. Box 22700, Amsterdam, 1100DD, The Netherlands , Amsterdam (Netherlands)
  • 4 Laboratory of Experimental Animal Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands , Amsterdam (Netherlands)
  • 5 The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands , Amsterdam (Netherlands)
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Publication Date
Dec 09, 2002
Volume
4
Issue
1
Pages
49–54
Identifiers
DOI: 10.1038/ni869
Source
Springer Nature
License
Yellow

Abstract

It has been proposed that HIV-1, in addition to directly infecting and killing CD4+ T cells, causes T cell dysfunction and T cell loss by chronic immune activation. We analyzed the effects of chronic immune activation in mice that constitutively expressed CD70, the ligand for the tumor necrosis factor receptor family member CD27, on B cells. CD70 transgenic (CD70 Tg) mice showed a progressive conversion of naive T cells into effector-memory cells, which culminated in the depletion of naive T cells from lymph nodes and spleen. T cell changes depended on continuous CD27-CD70 interactions and T cell antigen receptor stimulation. Despite this hyperactive immune system, CD70 Tg mice died aged 6–8 months from Pneumocystis carinii infection, a hallmark of T cell immunodeficiency. Thus, persistent delivery of costimulatory signals via CD27-CD70 interactions, as may occur during chronic active viral infections, can exhaust the T cell pool and is sufficient to induce lethal immunodeficiency.

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