Immune exhaustion in HIV infection

As HIV disease progresses in a person infected with the HIV virus, a group of cells in the immune system, the CD8+ T lymphocytes, become “exhausted,” losing many of their abilities to kill other cells infected by the virus. For many years scientists have debated whether this exhaustion of CD8+ T cells is the cause, or the consequence, of persistence of the HIV virus. In a study published this week in PLoS Medicine, Marcus Altfeld and colleagues studied the immune response over time amongst 18 individuals who had very recently become infected with HIV.

These researchers found that the presence of high amounts of HIV in the blood seemed to cause CD8+ T cell exhaustion; when antigen was reduced, either as a result of treatment with antiretroviral drugs, or evolution of viral epitopes to avoid recognition by CD8+ T cells, these epitope-specific CD8+ T cells recovered some of their original functions. These findings suggest that CD8+ T cell exhaustion is the consequence, rather than the cause, of persistent replication of HIV.

In a related article, Sarah Rowland-Jones and Thushan de Silva (from the Medical Research Council in Gambia), who were not involved in the study, discuss approaches to treat HIV efficiently by suppressing the viral load early in infection aimed at preserving HIV-1-specific immune function. They evaluate whether such strategies are likely to be practical.

Citation: Streeck H, Brumme ZL, Anastario M, Cohen KW, Jolin JS, et al. (2008) Antigen load and viral sequence diversification determine the functional profile of HIV-1– specific CD8þ T cells. PLoS Med 5(5):e100.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE

VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050100

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-05-altfeld.pdf

CONTACTS:
Sue McGreevey
Public Affairs Office
Massachusetts General Hospital
Boston, MA
+1 617 724-2764
smcgreevey@partners.org

Marcus Altfeld
Massachusetts General Hospital
Partners AIDS Research Center
149 13th Street
Boston, MA 02129
United States of America
+1 617-724-2461
+1 617-724-8586 (fax)
maltfeld@partners.org

Citation: Rowland-Jones S, de Silva T (2008) Resisting immune exhaustion in HIV-1 infection. PLoS Med 5(5): e103.

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PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-05-rowland-jones.pdf

CONTACT:
Sarah Rowland-Jones
Weatherall Institute of Molecular Medicine
MRC Human Immunology Unit
Radcliffe Hospital
Headley Way
Oxford, OX3 9DS
United Kingdom
+44 (1865) 222 316
+44 (1865) 222 502 (fax)
sarah.rowland-jones@ndm.ox.ac.uk

Frits Rosendaal and colleagues from Leiden University Medical Center show that the combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.

Citation: Meltzer ME, Lisman T, Doggen CJM, de Groot PG, Rosendaal FR (2008) Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on

the risk of a first venous thrombosis. PLoS Med 5(5): e97.

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VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050097

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-05-rosendaal.pdf

CONTACTS:
Frits R. Rosendaal
Leiden University Medical Center
Clinical Epidemiology and Hematology
PO Box 9600
Leiden, 2300 RC
Netherlands
+31 715 264 037
f.r.rosendaal@lumc.nl

PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org

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