News & Views in 2001

Although systemic viral infection gives rise to robust responses from both CD8⁺ and CD4⁺ T cells, there are striking differences as well as similarities in the way the two classes of lymphocyte cells react. Insights into the patterns of response by each type of T cell could lead to the development of new therapeutics that enhance or suppress factors governing CD8⁺ and CD4⁺ T-cell immunity. (pages 913–919)

Unequivocal evidence for the dynamic nature of mammalian mitochondria has been hard to find. However, the successful development of a transgenic mouse model carrying pathogenic mtDNA as reported here will cause us to take a fresh look at these dynamic organelles. (pages 934–940)

A mouse model for donor lymphocyte infusion reveals that a single immunodominant minor H antigen is responsible for the beneficial effects of donor T lymphocytes against host leukemia. Separating the good from the bad could mean the end of graft-versus-host disease in bone marrow transplants. (pages 789–794)

Recent insights into the receptors expressed by sensory neurons are providing the beginnings of a biological basis for designing therapies to block nociceptive information before it reaches the spinal cord. This approach could potentially avoid some of the side effects in the central nervous system caused by currently available analgesics. (pages 821–826)

The uptake of apoptotic CD40L⁺ cells by immature dendritic cells leads to dendritic-cell activation. This mechanism might account for the generation of autoreactive CD8⁺ T cells in HIV infection and indicates a general mechanism for the regulation of autoimmune T-cell responses during infection. (pages 807–813)

Mutation is one way in which RNA viruses evade the destructive actions of CD8⁺ cytotoxic lymphocytes. New research shows that they employ the same method to escape attack by CD4⁺ T cells. (pages 795–800)

The discovery of a family of proteins with strong homology to the uncoupling protein of brown fat has generated great interest as these molecules might represent therapeutic targets for human obesity. Two recent studies have used genetics to explore the role of one of these proteins, UCP2, in the control of mammalian metabolism and come to rather different conclusions.

Nicotine is widely used as an aid to smoking cessation and is being evaluated to treat non-smoking related disorders. Stimulation of angiogenesis by nicotine raises many questions about its mechanism of action and use in therapy. (pages 833–839)

The development of a sensitive in vitro method to amplify the pathological form of the prion protein might provide a tool for the pre-clinical diagnosis of prion diseases.

Better clinical endpoints are needed to monitor the efficacy of drugs designed to block enzymatic function, such as matrix metalloproteinase inhibitors. A new imaging technique allows researchers to monitor native enzymatic activity in vivo, and more effectively evaluate the therapeutic potential of these drugs (pages 743–748).

Artificial neural networks were used to decipher gene-expression signatures collected with DNA microarrays and to classify cancers into specific categories. Will this technology lead to better diagnostic tools and new therapeutic targets? (pages 673–679)

HIV isolates resistant to protease inhibitor treatment have an impaired ability to replicate in thymocytes, allowing T-cell production to continue despite the peripheral T-cell decline. Understanding the basis for cellular differences in HIV replication might teach us new ways to protect the immune system from highly pathogenic strains of HIV-1 (pages 712–718).

Mice with mutations in the Mer tyrosine kinase have deficits in the clearance of apoptotic thymocytes and increased titers of anti-DNA autoantibodies. These findings provide new in vivo evidence to suggest that impairments in clearance of apoptotic cells may underlie systemic autoimmunity.

Heme oxygenase-1, an enzyme expressed during injury, reduces vasoconstriction and inhibits formation of free radicals. Someday it might be used as a local therapeutic agent at sites of vascular injury (Pages 693–698).

The oligomeric structure of anthrax toxin might be exploited as a preventative or therapeutic vaccine.

The ability of all-trans-retinoic acid to stimulate granulocytic differentiation makes it useful in the treatment of acute promyelocytic leukemia. Recent findings suggest that this drug can also induce post-maturation apoptosis through the Apo-2L/TRAIL death ligand (pages 680–686).

The mutant proteins that cause polyglutamine disease bind CREB-binding protein (CBP), a key transcriptional co-activator for neuronal survival factors. This results in a loss of CBP-dependent transcription and may account for the neuronal degeneration associated with these diseases.