| First Author | Marques R | Year | 2009 |
| Journal | J Biol | Volume | 8 |
| Issue | 10 | Pages | 93 |
| PubMed ID | 19943952 | Mgi Jnum | J:203905 |
| Mgi Id | MGI:5529100 | Doi | 10.1186/jbiol194 |
| Citation | Marques R, et al. (2009) Generalized immune activation as a direct result of activated CD4+ T cell killing. J Biol 8(10):93 |
| abstractText | BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. |
