Assessment of the interlaboratory variability and robustness of JAK2V617F mutation assays: A study involving a consortium of 19 Italian laboratories.

To date, a plenty of techniques for the detection of JAK2V617F is used over different laboratories, with substantial differences in specificity and sensitivity. Therefore, to provide reliable and comparable results, the standardization of molecular techniques is mandatory.A network of 19 centers was established to 1) evaluate the inter- and intra-laboratory variability in JAK2V617F quantification, 2) identify the most robust assay for the standardization of the molecular test and 3) allow consistent interpretation of individual patient analysis results.

Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice.

Accumulating evidence favors a role for proinsulin as a key autoantigen in diabetes. In the mouse, two proinsulin isoforms coexist. Most studies point to proinsulin 2 as the major isoform recognized by T cells in the NOD mouse.

IL-15 availability conditions homeostasis of peripheral natural killer T cells.

Steady-state numbers of peripheral lymphocyte are tightly controlled. For conventional T cells, signals delivered through the interaction of the T cell receptor (TCR) with antigen-loaded MHC molecules are required for the peripheral survival of naive T cells and for their homeostatic expansion in lymphopenic hosts. Cytokines, including IL-7, are also essential for survival of peripheral naive T cells.

NKT cells inhibit the onset of diabetes by impairing the development of pathogenic T cells specific for pancreatic beta cells.

To determine the precise regulatory effect of NKT cells on CD4(+) T cells involved in autoimmune diabetes, we developed an in vivo model in which transferred naive transgenic T cells are stimulated by their antigen in the presence or absence of NKT cells or in the presence of another conventional transgenic alphabeta T cell. The presence of NKT cells did not block the initial activation and expansion of the CD4(+) T cells but did inhibit their IL-2 and IFN-gamma production and later proliferation, resulting in an anergic phenotype. These CD4(+) T cells did not induce significant insulitis and were unable to destroy the beta cells.

Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice.

Although deficiencies in the NKT cell population have been observed in multiple sclerosis and mouse strains susceptible to experimental autoimmune encephalomyelitis (EAE), little is known about the function of these cells in CNS autoimmunity. In this work we report that TCR Valpha14-Jalpha281 transgenic nonobese diabetic mice, which are enriched in CD1d-restricted NKT cells, are protected from EAE. The protection is associated with a striking inhibition of Ag-specific IFN-gamma production in the spleen, implying modulation of the encephalitogenic Th1 response.

Phenotypic and functional differences between NKT cells colonizing splanchnic and peripheral lymph nodes.

NKT cells are considered unconventional T cells. First, they are restricted by a nonclassical MHC class I molecule, CD1d, which presents glycolipids; second, their TCR repertoire is very limited. After stimulation by their TCR, NKT cells rapidly release large amounts of cytokines, such as IL-4 and IFN-gamma.