O que nós ainda não sabemos sobre a AIDS

sábado, novembro 28, 2009

What we still don't know about AIDS

Miranda Robertson

Journal of Biology 2009, 8:87doi:10.1186/jbiol200

Published: 27 November 2009

First paragraph (this article has no abstract)

A great deal is known about the human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS) [1], one of whose cardinal features is its exquisite adaptation to its human host. It enters the body through damaged epithelia, or more insidiously, through specialized cells (M cells) in the intestinal epithelium whose function is to deliver viruses and bacteria to waiting immune cells in the tissue below. There, the virus binds to a specialized receptor on the surface of one of these cells - the dendritic cells, which play a central part in activating the CD4+ T lymphocytes whose destruction by the virus ultimately and lethally disables the immune system. Recognition of the bound virus causes the dendritic cell to migrate to the lymphoid tissues where it engages with the CD4+ T lymphocytes that it activates. This enables the virus to bind to molecules on the surface of the T cell - a highly specific interaction involving the CD4 molecules that give CD4+ T cells their name and that enables the virus to enter the cell. Once the virus is inside the cell, it produces DNA copies of its genome that integrate into the host DNA where cellular transcriptional regulators specifically induced by activation of CD4+ T cells are instrumental in activating transcription of the viral genome to produce more viruses.



Life and death as a T lymphocyte: from immune protection to HIV pathogenesis

Nienke Vrisekoop* , Judith N Mandl* and Ronald N Germain

Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr MSC-1892, Bethesda, MD, USA

author email corresponding author email* Contributed equally

Journal of Biology 2009, 8:91doi:10.1186/jbiol198

Published: 27 November 2009


Detailed analysis of T cell dynamics in humans is challenging and mouse models can be important tools for characterizing T cell dynamic processes. In a paper just published in Journal of Biology, Marques et al. suggest that a mouse model with its activated CD4+ T cells are deleted has relevance for HIV infection.



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

Rute Marques1, Adam Williams2,5, Urszula Eksmond1, Andy Wullaert3, Nigel Killeen4, Manolis Pasparakis3, Dimitris Kioussis2 and George Kassiotis1

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

2Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK

3Institute for Genetics, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany

4Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA

5Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA

author email corresponding author email

Journal of Biology 2009, 8:93doi:10.1186/jbiol194

Published: 27 November 2009


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.