JCI table of contents August 1, 2005

July 07, 2005


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

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


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

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


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

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


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

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

JCI Journals

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.