Hot off the presses! Jun 01 Nat Rev Immunol

The Jun 01 issue of the Nat Rev Immunol is now up on Pubget (About Nat Rev Immunol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• From the editors
  - Nat Rev Immunol 9(6):385 (2009)
  
• Neuroimmunology: Finding a way into the brain
  - Nat Rev Immunol 9(6):386 (2009)
  
• T cell differentiation: The TH1 two step
  - Nat Rev Immunol 9(6):387 (2009)
  
• Cladribine hope for multiple sclerosis
  - Nat Rev Immunol 9(6):387 (2009)
  
• T cells: Helper cell metamorphosis
  - Nat Rev Immunol 9(6):388 (2009)
  
• Tumour immunology: Attacking the enabler
  - Nat Rev Immunol 9(6):388 (2009)
  
• In brief: Immunogenetics, Parasite immunity, Neuroimmunology
  - Nat Rev Immunol 9(6):388 (2009)
  
• In brief: Parasite immunity, Autoimmunity, Lymphocyte migration
  - Nat Rev Immunol 9(6):389 (2009)
  
• Autoimmunity: A new target in multiple sclerosis?
  - Nat Rev Immunol 9(6):390 (2009)
  
• Inflammation: Targeting TNF
  - Nat Rev Immunol 9(6):390 (2009)
  
• Neuroimmunology: Basement membrane laminins guard the CNS
  - Nat Rev Immunol 9(6):391 (2009)
  
• T cell memory: A new resting place
  - Nat Rev Immunol 9(6):392 (2009)
  
• Antiviral immunity: IL-21: in it for the long run
  - Nat Rev Immunol 9(6):392 (2009)
  
• Autoimmune T cell responses in the central nervous system
  - Nat Rev Immunol 9(6):393-407 (2009)
  Autoreactive T cell responses have a crucial role in central nervous system (CNS) diseases such as multiple sclerosis. Recent data indicate that CNS autoimmunity can be mediated by two distinct lineages of CD4+ T cells that are defined by the production of either interferon-gamma or interleukin-17. The activity of these CD4+ T cell subsets within the CNS influences the pathology and clinical course of disease. New animal models show that myelin-specific CD8+ T cells can also mediate CNS autoimmunity. This Review focuses on recent progress in delineating the pathogenic mechanisms, regulation and interplay between these different T cell subsets in CNS autoimmunity.
• From genes to function: the next challenge to understanding multiple sclerosis
  - Nat Rev Immunol 9(6):408-417 (2009)
  Susceptibility to multiple sclerosis is jointly determined by genetic and environmental factors, and progress has been made in defining some of these genetic associations, as well as their possible interactions with the environment. However, definitive proof for the involvement of specific genetic determinants in the disease will only come from studies that examine their functional roles in disease pathogenesis. New and combined approaches are needed to analyse the complexity of gene regulation and the functional contribution of each genetic determinant to disease susceptibility or pathophysiology. These studies should proceed in parallel with the use of genetically defined human populations to explore how both genetic and environmental factors affect the function of the pathways in individuals with and without disease, and how these determine the inherited risk of multiple sclerosis.
• Reflex control of immunity
  Tracey KJ - Nat Rev Immunol 9(6):418-428 (2009)
  Inflammation can cause damage and even death. What controls this primitive and potentially lethal innate immune response to injury and infection? Molecular and neurophysiological studies during the past decade have revealed a pivotal answer: immunity is coordinated by neural circuits that operate reflexively. The afferent arc of the reflex consists of nerves that sense injury and infection. This activates efferent neural circuits, including the cholinergic anti-inflammatory pathway, that modulate immune responses and the progression of inflammatory diseases. It might be possible to develop therapeutics that target neural networks for the treatment of inflammatory disorders.
• Regulation of innate immune responses in the brain
  Rivest S - Nat Rev Immunol 9(6):429-439 (2009)
  Microglial cells are the main innate immune cells of the complex cellular structure of the brain. These cells respond quickly to pathogens and injury, accumulate in regions of degeneration and produce a wide variety of pro-inflammatory molecules. These observations have resulted in active debate regarding the exact role of microglial cells in the brain and whether they have beneficial or detrimental functions. Careful targeting of these cells could have therapeutic benefits for several types of trauma and disease specific to the central nervous system. This Review discusses the molecular details underlying the innate immune response in the brain during infection, injury and disease.
• A molecular trio in relapse and remission in multiple sclerosis
  - Nat Rev Immunol 9(6):440-447 (2009)
  Two thirds of patients with multiple sclerosis have the relapsing-remitting form, which often progresses to more debilitating disease. Striking clinical recovery, termed remission, often follows these periodic neurological defects, termed relapses. Recent work has revealed the role of three key molecules in relapse and remission: alpha4beta1 integrin (also known as VLA4) is an adhesion molecule that mediates T cell migration from the blood into the brain; osteopontin binds to alpha4beta1 integrin, stimulating the production of pro-inflammatory cytokines and inhibiting apoptosis; and alphaB crystallin inhibits inflammation in the brain. This Review discusses how this molecular trio interacts to initiate relapses (in the case of osteopontin and alpha4beta1 integrin) and then to terminate them as remissions in multiple sclerosis (in the case of alphaB crystallin).
• Losing your nerves? Maybe it's the antibodies
  - Nat Rev Immunol 9(6):449-456 (2009)
  We propose that the normal immunocompetent B cell repertoire is replete with B cells making antibodies that recognize brain antigens. Although B cells that are reactive with self antigen are normally silenced during B cell maturation, the blood–brain barrier (BBB) prevents many brain antigens from participating in this process. This enables the generation of a B cell repertoire that is sufficiently diverse to cope with numerous environmental challenges. It requires, however, that the integrity of the BBBs is uninterrupted throughout life to protect the brain from antibodies that crossreact with microorganisms and brain antigens. Under conditions of BBB compromise, and during fetal development, we think that these antibodies can alter brain function in otherwise healthy individuals.