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J Biol. 2009;8(10):93. doi: 10.1186/jbiol194.

Generalized immune activation as a direct result of activated CD4+ T cell killing.

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  • 1Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.



In addition to progressive CD4(+) T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity.


Here we report that, in a virus-free mouse model, conditional ablation of activated CD4(+) T cells, the targets of immunodeficiency viruses, accelerates their turnover and produces CD4(+) T cell immune deficiency. More importantly, activated CD4(+) T cell killing also results in generalized immune activation, which is attributable to regulatory CD4(+) T cell insufficiency and preventable by regulatory CD4(+) T cell reconstitution. Immune activation in this model develops independently of microbial exposure. Furthermore, microbial translocation in mice with conditional disruption of intestinal epithelial integrity affects myeloid but not T cell homeostasis.


Although neither ablation of activated CD4(+) T cells nor disruption of intestinal epithelial integrity in mice fully reproduces every aspect of HIV-associated immune dysfunction in humans, ablation of activated CD4(+) T cells, but not disruption of intestinal epithelial integrity, approximates the two key immune alterations in HIV infection: CD4(+) T cell immune deficiency and generalized immune activation. We therefore propose activated CD4(+) T cell killing as a common etiology for both immune deficiency and activation in HIV infection.

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