Yvonne Kern

The elimination of Anaplasma phagocytophilum requires CD4+ T cells, but is independent of Th1 cytokines and a wide spectrum of effector mechanisms

Anaplasma phagocytophilum is a Gram‐negative, obligate intracellular bacterium that exhibits a striking tropism for neutrophils. When we depleted mice of neutrophils, we found that murine susceptibility to anaplasmal infection was dependent on their presence. While serving as sites of bacterial replication, neutrophils do not seem to act as efficient killer cells in A. phagocytophilum infection, because mice deficient for antimicrobial effectors of neutrophils such as myeloperoxidase, granulocyte elastase, and cathepsin G were fully competent in pathogen elimination. To identify components of the immune system other than neutrophils that control A. phagocytophilum, we studied the course of infection in several gene‐deficient mouse strains. IFN‐γ production by NK cells was important for initial defense, but not critical for pathogen elimination. In contrast, bacterial clearance was strictly dependent on CD4+ T cells, but unexpectedly achieved in the absence of perforin, Fas/FasL and major Th1 cytokines such as IL‐12, IFN‐γ, and MCP‐1. These findings provide a novel paradigm for the control of an intracellular pathogen, which appears to be strikingly different from the CD4+ T cell‐, IL‐12‐, and IFN‐γ‐dependent immunity to other intracellular bacteria.

Inhibition of corneal inflammation following keratoplasty by birch leaf extract.

The objective of this study was to determine the effect of birch leaf (Betula pendula) extract (BPE) on corneal inflammation following keratoplasty in the rat model. T cells were stimulated in vitro in the presence of BPE. Proliferation, activation phenotype and the number of apoptotic/necrotic cells in cell culture were analyzed by flow cytometry. Corneal transplantation was performed between Fisher and Lewis rats. Recipient rats were either treated with cyclosporine A at a low dosage (Low-dose CsA=LDCsA) or received LDCsA in combination with BPE (2×1ml/day). Clinical signs for corneal inflammation and rejection time points were determined. Infiltrating leukocytes were analyzed histologically. BPE specifically inhibited T cell proliferation in vitro by inducing apoptosis. The phenotype was not affected. In vivo, BPE significantly delayed the onset of corneal opacification (p<0.05). The amount of infiltrating CD45(+) leukocytes and CD4(+) T cells (p<0.001) was significantly reduced by BPE, whereas infiltration of CD163(+) macrophages was not significantly different between the two groups. BPE selectively induces apoptosis of activated T cells. Accordingly, BPE treatment significantly reduces infiltrating T cells and subsequent corneal opacification following keratoplasty. Our findings suggest BPE as a promising anti-inflammatory drug to treat corneal inflammation.