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

First Author  Tesselaar K Year  2003
Journal  Nat Immunol Volume  4
Issue  1 Pages  49-54
PubMed ID  12469117 Mgi Jnum  J:82292
Mgi Id  MGI:2652005 Doi  10.1038/ni869
Citation  Tesselaar K, et al. (2003) Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol 4(1):49-54
abstractText  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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