HIV-1 causes T cell loss by directly infecting and killing CD4+ T cells, but this process alone does not explain the severity of the immunodeficiency. Additional mechanisms such as chronic immune stimulation have been implicated, but their involvement has been unproven. In December 9 Nature Immunology, Kiki Tesselaar and colleagues from Academic Medical Center, Amsterdam, The Netherlands, show that chronic costimulation of the immune system via CD27-CD70 interactions induces lethal T cell immunodeficiency (Nature Immunology, doi:10.1038/ni869, December 9, 2002).

Tesselaar et al. used mice that constitutively expressed CD70 — the ligand for the tumor necrosis factor receptor family member CD27 — on B cells. They observed that chronic activation of CD27 in these mice was followed by progressive conversion of naive T cells into effector-memory cells, leading to the depletion of naive T cells from lymph nodes and spleen. In addition, they showed that...

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