In this issue.
June 28th, 2008 | by admin |In this issue.
COVER PICTURES: The cover shows a confocal micrograph of myelinated nervous tissue at the rim of a demyelinating lesion in the brain white matter of a patient with multiple sclerosis (MS). Myelin surrounding the axon is stained by a monoclonal antibody obtained by recombinant expression of immunoglobulin genes from clonally expanded plasma cells as present in the cerebrospinal fluid of MS patients. The image was taken from the article by von Büdingen et al. (pp.2014-2023) in which the authors demonstrate that myelin specific antibodies result from antigen driven immune responses found in the cerebrospinal fluid of MS patients. TH17 FOUND GUILTY OF YET ANOTHER CRIME …: pp. 1877-1888The ever expanding repertoire of diseases associated with Th17 has just added another to its family. In this issue, Shi and colleagues detail the involvement of Th17 in the induction of the B cell-mediated autoimmune disease, autoimmune myasthenia gravis (EAMG). In this disease model, inflammatory stimuli recruit CD11b(+) cells into the draining lymph nodes; a phenomenon that is dependent on the chemokine CCL2. Inside the lymph nodes, the CD11b(+) cells present autoantigen to naïve T cells in a milieu of IL-6 and various growth factors, polarizing T cells into the Th17 phenotype. These Th17 cells then facilitate the production of high titres of pathogenic anti-acetylcholine receptor IgG2b antibodies, which are ultimately responsible for disease pathology. HELPER CELLS TURN THE KEY TO CTL MEMORY: THE ROLE OF CD27: pp. 1847-1856CD8(+) T cells are a key component of the host adaptive immune response against viruses. Once the primary infection is controlled, the CTL population declines but a small population of memory cells persists and acts as a sentinel of the immune system. In recent years it has been determined that CD4(+) T cells play a vital role in the survival and functional responsiveness of memory CD8(+) T cells; however, the mechanism(s) of this interaction is(are) still unclear. In this issue, Matter et al. demonstrate that CD4(+) T cells help sustain CTL memory by retaining CD27 expression on CD8(+) T cells. CD27 signalling in memory CTL during secondary stimulation results in the autocrine secretion of IL-2 and is crucial for an optimal secondary expansion. Therefore, CD4(+) T cells help memory CD8(+) T cell function by regulating CD27 expression. UNLIKELY COLLABORATORS: IMMUNOTHERAPY AND RADIOTHERAPY: pp. 1937-1947It appears that the immunotherapy versus radiotherapy debate has finally reached a happy ending. In this issue, Avogadri et al. demonstrate that low dose irradiation facilitates the anti-tumour effect of live attenuated Salmonella typhimurium injections. Intra-tumour injection of S. typhimurium induces a proinflammatory environment within the tumour that enhances endogenous antigen presentation by dendritic cells in the tumour draining lymph node, which in turn leads to more activated tumor-specific effector CTL. The anti-tumour activity is further boosted by low dose irradiation at a distal tumour site, which was not treated with bacteria. Thus, immunotherapy and radiotherapy are not necessarily incompatible in the treatment of cancer, but are in fact synergistic treatment options. IMMUNE DYSREGULATION IN ASTHMA: WHEN THE KILLERS STRIKE: pp. 2034-2045Despite the reported antagonistic roles of natural regulatory T cells (Treg) and CD4(+) invariant NKT (iNKT) cells in immunoregulatory networks of allergic asthma, no evidence for an interaction between these two cell subsets has been observed. In this issue, Nguyen et al. demonstrate that CD4(+) iNKT cells from allergic asthmatic subjects exhibit increased cytotoxicity against autologous Treg as compared with CD4(+) iNKT cells from healthy subjects. The selective killing of Treg by CD4(+) iNKT occurs via a cell death pathway that employs the pore-forming molecule, perforin, and the cytotoxic enzyme, granzyme B. Together the data suggest a potential involvement of this aberrant cellular interaction in the pathobiology of allergic asthma. TYPE I INTERFERON AND PDC IN SJöGREN\’S SYNDROME: pp. 2024-2033Primary Sjögren\’s Syndrome (pSjS) is an autoimmune disease that affects the salivary and lachrymal glands and results in debilitating systemic complaints such as extreme fatigue and arthralgia. In order to effectively treat these systemic symptoms, one must first understand its underlying cause. In this issue, Wildenberg et al. use gene expression profiling to address this aspect of the disease, and demonstrate that the activity of the type I interferon system is elevated systemically in pSjS patients. This activity is specifically caused by IFN-beta and correlates with an increased activation of peripheral plasmacytoid DC (pDC). Given that the systemic symptoms of pSjS are reminiscent of those found in type I interferon-treated patients, type I interferon is the likely culprit. This study expands on the role of type I interferon and pDC in pSjS and highlights a possible new therapeutic target. FROM OUR SISTER JOURNALS - LABEL-FREE CELL-BASED ASSAYS FOR DRUG DISCOVERY: Conventional label and reporter-based cell assays may be prone to artifacts due to considerable manipulation of the cell either by labeling or overexpression of targets or reporter proteins. Cell-based label-free technologies preclude the need for cellular labelling or over expression of reporter proteins, utilizing the inherent morphological and adhesive characteristics of the cell as a physiologically relevant and quantitative readout for various cellular assays. Furthermore, these technologies utilize non-invasive measurements allowing for time resolution and kinetics in the assay. In this article, researchers from San Diego (CA, USA) review the various label-free technologies that are being used in both basic research and drug discovery settings.Xi, B. et al., Biotechnol. J. 2008. 3: 484-495.