JCI table of contents August 1, 2005

July 07, 2005

EDITOR'S PICK

HIV domains take on new functions in mediating immunity

HIV is able to evade the host immune system to cause infection. In particular, HIV downregulates CD4+ immune T cell function, which might aid infection, but the mechanisms underlying this phenomenon are unknown. In a study appearing online on July 7 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Yechiel Shai and colleagues from the Weizmann Institute examine the fusion peptide (FP) of HIV.

The researchers show that the FP plays two roles in HIV infection - it works with other domains to mediate fusion of the virus with the cell membrane, while also downregulating the T cell responses that normally would block infection.

The authors show that the HIV FP can co-localize with CD4 and T cell receptor in T cells, and inhibits antigen-specific T cell proliferation. This data highlights a potential immunosuppressive activity specific to HIV infection.

The authors then extend their findings by exploiting the activity of FP and show that it ameliorates the autoimmune disease adjuvant arthritis in rats. This study not only adds to our understanding of the mechanisms of HIV pathogenesis, but it also shows that the FP molecule, independent of HIV, may provide a novel way to decrease undesirable immune responses.

Title: HIV-1 Fusion Peptide Targets the TCR and Inhibits Antigen-Specific T-Cell Activation

AUTHOR CONTACT:
Yechiel Shai
Weizmann Institute of Science, Rehovot, Israel
Phone: 972-893-42-711; Fax: 972-893-44-112; E-mail: Yechiel.Shai@weizmann.ac.il

View the PDF of this article at: https://www.the-jci.org/article.php?id=23956

METABOLIC DISEASE

Fat cells and cholesterol: The plot thickens


Fat tissue, in addition to its role in energy storage, also accumulates cholesterol. But little is known about how fat cells metabolize cholesterol. Now in a study appearing online on July 7 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Mitchell Lazar and colleagues from the University of Pennsylvania show that treating fat cells with ligands of a receptor called PPAR gamma induces expression of the oxidized LDL receptor 1 (OLR1). OLR1 mediates cholesterol levels in the fat cells.

This is the first description of OLR1 expression in fat tissue. OLR1 is shown to regulate uptake of the "good" cholesterol called LDL. The fact that OLR1 has been identified as a PPAR gamma regulated gene provides evidence that oxidized LDL may be involved in fat cell metabolism. The observation suggests that anti-diabetic drugs that are also PPAR gamma ligands may be beneficial in individuals with metabolic syndrome/ insulin resistance by enhancing lipid uptake into the adipocytes and suppressing release of inflammatory factors.

Title: PPAR gamma Regulates Adipocyte Cholesterol Metabolism Via Oxidized LDL Receptor 1

AUTHOR CONTACT:
Mitchell A. Lazar
University of Pennsylvania, Philadelphia, PA USA
Phone: 215-898-0198; Fax: 215-898-5408; E-mail: lazar@mail.med.upenn.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=24130

IMMUNOLOGY

Regulatory T cell subset: New, natural, and naive


The CD4+ CD25+ subset of immune T cells is found in the thymus and periphery, and has immune suppressive capacity. While the thymic origin of the cells is accepted, its developmental pathway has remained elusive. Peripheral CD4+ CD25+ T cells have been reported to belong to the antigen-experienced T cell compartment, to be unresponsive to stimulation, to have poor proliferative potential, and to be prone to cell death. How can a population of cells with such characteristics control self-reactivity in humans?

In a study appearing online on July 7 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Danila Valmori and colleagues from Columbia University analyze CD25 expression in human circulating CD4+ T lymphocytes, with respect to their differentiation. They have identified a subset of CD25+ cells contained in a naïve fraction. They named this subset natural naive (Nn) Tregs and they can be found in all individuals, but are more prominent in young adults than in the elderly. NnTregs have most naïve characteristics and a highly increased proliferative potential as compared to the previously defined antigen-experienced Tregs, but, similar to these latter, are anergic ex-vivo and exert suppressor functions.

NnTregs represent a pure population of naïve naturally-occurring regulatory T cells, whereas Tregs are most likely composed of a mixture of NnTreg-derived antigen-experienced regulatory T cells, recently activated CD4+ T cells, and, possibly, other regulatory subsets derived from the CD4+CD25- population.

Title: A peripheral circulating compartment of natural naïve CD4+ Tregs

AUTHOR CONTACT:
Danila Valmori
Columbia University, New York, NY USA
Phone: 212-305-3923; Fax: 212-305-7348; E-mail: dv2117@columbia.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=23963

NEUROLOGY

Stepping up therapy for stroke and other CNS disorders


Stroke is a major medical problem, with only very limited treatment options. In a study appearing online on July 7 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Armin Schneider and colleagues from Axaron Biosciences describe new roles for granulocyte colony-stimulating factor (G-CSF) in treating stroke and other central nervous system roles of this protein.

The team reports that G-CSF has potent cell protective effects on mature neurons, explaining why it has been shown to be useful in animal stroke models. Moreover, G-CSF drives neuronal differentiation of adult neural stem cells in the brain, and has profound impact on long-term functional outcome after cerebral ischemia. The authors show that G-CSF itself is a neuronally expressed protein in the brain, and that systemic G-CSF can penetrate the intact blood-brain-barrier.

Thus, G-CSF is a potentially novel treatment for stroke and neurodegeneration. G-CSF doubles hippocampal neurogenesis even in normal, non-ischemic animals, making it a potential drug candidate for diseases where disturbances in neurogenesis are a factor.

Title: The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis

AUTHOR CONTACT:
Armin Schneider
Axaron Bioscience, Heidelberg, Germany
Phone: 049-622-145-4713; E-mail: schneider@axaron.de

View the PDF of this article at: https://www.the-jci.org/article.php?id=23559
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