NEUROBIOLOGY: Propagating a characteristic of Parkinson disease

The nerve cells affected in individuals with Parkinson disease are characterized by the presence of structures known as Lewy bodies, which are primarily composed of aggregated α-synuclein (α-syn). Recent data, have suggested that α-syn can be transferred between neurons and that this propagates disease. A team of researchers, led by Patrik Brundin, at Lund University, Sweden, has now tested this hypothesis in several coculture systems and in vivo models, generating data that indicate that it is a key element in the progression of Parkinson disease pathology.

TITLE: Alpha-synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells

TRANSPLANTATION: Identifying the immune cell barrier to fetal stem cell transplantation

It is hoped that stem cell transplantation might provide a new approach to treat inherited disorders. However, this approach is currently limited by graft rejection and the need to persistently use immunosuppressive drugs to prevent graft rejection. Transplantation of genetically correct stem cells from a genetically nonidentical individual into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome these limitations. However, clinical use of IUHCTx has been hampered by poor engraftment. Tippi MacKenzie, Qizhi Tang, and colleagues, at UCSF, San Francisco, have now determined that in mice maternal immune cells known as T cells are the main barrier to engraftment following IUHCTx. When the graft used for the IUHCTx was matched to the mother, engraftment was markedly enhanced, leading the authors to suggest that the clinical success of IUHCTx may be improved by transplanting cells matched to the mother.

TITLE: Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

TUMOR IMMUNOLOGY: New immune cell activator protects mice from cancer

Activation of immune cells known as iNKT cells has been shown to protect against cancer in animal models. In these studies, iNKT cell activation is achieved using a molecule known as alpha-GalCer and protection is mediated primarily by the immune molecule IFN-gamma. However, a team of researchers, led by Jay Berzofsky and Masaki Terabe, at the National Institutes of Health, Bethesda, has now identified a new iNKT cell activator that protects mice from tumors through an IFN-gamma-independent mechanism. As this new activator (beta-ManCer) synergized with alpha-GalCer to protect mice against tumors, the authors suggest that similar treatments may provide protection against tumors in humans.

TITLE: Mouse and human iNKT cell agonist beta-mannosylceramide reveals a distinct mechanism of tumor immunity

VIROLOGY: Homing in on the virus-infected cells that cause a fatal B cell tumor

Multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL) are fatal tumors; current treatments prolong survival by a few years at best. These tumors arise from immune cells known as B cells and are caused by Kaposi sarcoma-associated herpesvirus (KSHV). Little is known about the identity of the B cell subtypes most susceptible to infection by KSHV, information that would provide invaluable insight into the development of these fatal tumors. In this context, Dean Kedes and colleagues, at the University of Virginia Health Systems, Charlottesville, have now identified a subset of human tonsillar cells as susceptible to infection with KSHV. Their data lead them to suggest that KSHV latently (silently) infects tonsillar IgM-lambda-expressing B cells, which then proliferate and acquire characteristics similar to those of the tumor cells in individuals with MCD.

TITLE: KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation

Ushma Neill
Journal of Clinical Investigation

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