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

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

Authors :
Jannie Borst
Paul A. Baars
René A. W. van Lier
Gijs M.W. van Schijndel
Marinus H. J. van Oers
Kiki Tesselaar
Martin van der Valk
Ramon Arens
Clinical Haematology
AII - Amsterdam institute for Infection and Immunity
Experimental Immunology
Source :
Nature immunology, 4(1), 49-54. Nature Publishing Group
Publication Year :
2002
Publisher :
Springer Science and Business Media LLC, 2002.

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.

Details

ISSN :
15292916 and 15292908
Volume :
4
Database :
OpenAIRE
Journal :
Nature Immunology
Accession number :
edsair.doi.dedup.....b250c11e8b19e7e12d6dca19de450b30
Full Text :
https://doi.org/10.1038/ni869