Effector memory T­cells in the pathogenesis of ANCA-associated vasculitides.

Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory T­cells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including T­helper type 1 (Th1) CD4+ T­cells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory T­cells is skewed towards an increase of Th2 type, Th17, and Th22 cell fractions in GPA. Anomalous effector memory CD4+ T­cell co-stimulation is suggested by the aberrant expression of P­selectin glycoprotein ligand-1, ß­2 integrin, chemokine receptors, natural-killer group 2 member D (NKG2D) and other activating receptors. The increased expression of these receptors is accompanied by T­cell activation and migration to inflamed tissues. T­cells are abundant and secrete proinflammatory cytokines in inflammatory lesions in AAV. The T­cell mediated tissue damage correlates with renal outcome, whereas B­cell infiltration does not. Activation of lesional CD4+NKG2D+ effector memory T­cells is independent of the antigen; moreover, CD4+NKG2D+ effector memory T­cells display NK-cell-like cytotoxicity towards microvascular endothelial cells in vitro. Thus, effector memory T­cells play an important role in tissue damage and disease progression in AAV. Sequentially administered or combined with B­cell depleting therapy, T­cell-directed therapies, especially those directed against effector memory CD4+ T­cells, may further improve the outcome and help to achieve long-term remissions in AAV.

[Effector memory T­cells in the pathogenesis of ANCA-associated vasculitides. German version]. / Effektor-Memory-T­Zellen in der Pathogenese von ANCA-assoziierten Vaskulitiden.

Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory T­cells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including T­helper type 1 (Th1) CD4+ T­cells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory T­cells is skewed towards an increase of Th2 type, Th17 and Th22 cell fractions in GPA. Anomalous effector memory CD4+ T­cell co-stimulation is suggested by the aberrant expression of P­selectin glycoprotein ligand­1, beta­2 integrin, chemokine receptors, natural-killer group 2 member D (NKG2D) and other activating receptors. The increased expression of these receptors is accompanied by T­cell activation and migration to inflamed tissues. The T­cells are abundant and secrete proinflammatory cytokines in inflammatory lesions in AAV. The T­cell mediated tissue damage correlates with renal outcome, whereas B-cell infiltration does not. Activation of lesional CD4+NKG2D+ effector memory T­cells is independent of the antigen; moreover, CD4+NKG2D+ effector memory T­cells display NK-cell-like cytotoxicity towards microvascular endothelial cells in vitro. Thus, effector memory T­cells play an important role in tissue damage and disease progression in AAV. Sequentially administered or combined with B-cell depleting therapy, T­cell-directed therapies, especially those directed against effector memory CD4+ T­cells, may further improve the outcome and help to achieve long-term remission in AAV.

Prandtl-number dependence of turbulent flame propagation.

Inertial-range cascade phenomenology is used to predict Prandtl-number (Pr) dependencies of turbulent flame properties. A unified picture of turbulent flame structure and burning velocity is developed that encompasses all Pr regimes. Implications of the analysis for gaseous flames (Pr near unity), autocatalytic fronts in liquids (high Pr), and astrophysical flames (low Pr) are noted.

Kinematics of small scale anisotropy in turbulence.

A simple, empirically motivated model is proposed to explain the transfer of imposed large scale anisotropy to small scales in high-Reynolds-number turbulence. Observed power-law scalings of anisotropy metrics are interpreted as manifestations of power-law scalings governing high-gradient regions resulting from compressional eddy motions. The model is used to interpret the measured moment-order dependencies of the exponents and amplitudes of odd-order structure functions and derivative moments that vanish in the absence of anisotropy.

Imaging a conserved scalar in gas mixing by means of a linear spark.

A straight filamentary spark produced by a laser has been used to image the spatial distribution of gases in a jet of methane in air. The technique provides a direct map of a conserved scalar quantity useful in modeling turbulent reacting flows and may have other experimental advantages.