73 research outputs found
Enhanced inverse bremsstrahlung heating rates in a strong laser field
Test particle studies of electron scattering on ions, in an oscillatory
electromagnetic field have shown that standard theoretical assumptions of small
angle collisions and phase independent orbits are incorrect for electron
trajectories with drift velocities smaller than quiver velocity amplitude. This
leads to significant enhancement of the electron energy gain and the inverse
bremsstrahlung heating rate in strong laser fields. Nonlinear processes such as
Coulomb focusing and correlated collisions of electrons being brought back to
the same ion by the oscillatory field are responsible for large angle, head-on
scattering processes. The statistical importance of these trajectories has been
examined for mono-energetic beam-like, Maxwellian and highly anisotropic
electron distribution functions. A new scaling of the inverse bremsstrahlung
heating rate with drift velocity and laser intensity is discussed.Comment: 12 pages, 12 figure
Nucleotide-Oligomerization-Domain-2 Affects Commensal Gut Microbiota Composition and Intracerebral Immunopathology in Acute Toxoplasma gondii Induced Murine Ileitis
Background Within one week following peroral high dose infection with
Toxoplasma (T.) gondii, susceptible mice develop non-selflimiting acute
ileitis due to an underlying Th1-type immunopathology. The role of the innate
immune receptor nucleotide-oligomerization-domain-2 (NOD2) in mediating
potential extra-intestinal inflammatory sequelae including the brain, however,
has not been investigated so far. Methodology/Principal Findings Following
peroral infection with 100 cysts of T. gondii strain ME49, NOD2-/- mice
displayed more severe ileitis and higher small intestinal parasitic loads as
compared to wildtype (WT) mice. However, systemic (i.e. splenic) levels of
pro-inflammatory cytokines such as TNF-α and IFN-γ were lower in NOD2-/- mice
versus WT controls at day 7 p.i. Given that the immunopathological outcome
might be influenced by the intestinal microbiota composition, which is shaped
by NOD2, we performed a quantitative survey of main intestinal bacterial
groups by 16S rRNA analysis. Interestingly, Bifidobacteria were virtually
absent in NOD2-/- but not WT mice, whereas differences in remaining bacterial
species were rather subtle. Interestingly, more distinct intestinal
inflammation was accompanied by higher bacterial translocation rates to extra-
intestinal tissue sites such as liver, spleen, and kidneys in T. gondii
infected NOD2-/- mice. Strikingly, intracerebral inflammatory foci could be
observed as early as seven days following T. gondii infection irrespective of
the genotype of animals, whereas NOD2-/- mice exhibited higher intracerebral
parasitic loads, higher F4/80 positive macrophage and microglia numbers as
well as higher IFN-γ mRNA expression levels as compared to WT control animals.
Conclusion/Significance NOD2 signaling is involved in protection of mice from
T. gondii induced acute ileitis. The parasite-induced Th1-type immunopathology
at intestinal as well as extra-intestinal sites including the brain is
modulated in a NOD2-dependent manner
Low Coordinate, Monomeric Molybdenum and Tungsten(III) Complexes: Structure, Reactivity and Calculational Studies of (silox) 3
Urinary Metabolic Profiles of Inflammatory Bowel Disease in Interleukin-10 Gene-Deficient Mice
Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a mouse model of chronic intestinal inflammation
Intraepithelial lymphocytes (IELs) represent the first line of lymphocyte defense against the intestinal bacteria. Although previous studies have demonstrated a protective role of IELs in the development of colitis, the data supporting a regulatory role for IELs are limited. The objective of this study was to examine the suppressive activity of IELs in vitro and in vivo using a mouse model of chronic small and large bowel inflammation. Adoptive transfer of CD8α+ IELs isolated from small intestines of wild-type (WT) mice into TCR βxδ-deficient (TCR βxδ−/−) recipients did not prevent or delay the onset of the disease induced by WT CD4+CD45RBhigh T cells. On the contrary, we observed a more rapid onset of wasting and clinical signs of intestinal inflammation when compared with animals injected with CD4+CD45RBhigh T cells alone. Histopathological scores of small and large bowel did not differ significantly between the two groups. Transfer of IELs alone did not produce any pathological changes. Real-time PCR analysis of intestinal tissues showed up-regulation of message for Th1- and macrophage-derived cytokines in colon and small bowel. Using Foxp3-GFP reporter mice, we were unable to detect any Foxp3+ cells within the CD8α+ IELs but did find a small population of Foxp3+CD4+ IELs in the small and large bowel. Using in vitro suppression assay, we found that neither TCRαβ+CD8αα+, TCRαβ+CD8αβ+ nor TCRγδ+CD8αα+ IELs were capable of suppressing CD4+ T-cell proliferation. Taken together, our data do not support an immunoregulatory role for CD8α+ IELs in a mouse model of small and large bowel inflammation
Human small intestinal mucosa harbours a small population of cytolytically active CD8(+) αβ T lymphocytes
Intraepithelial lymphocytes (IEL) in normal human small intestine exhibit cytotoxicity. This study was undertaken to characterize the effector cells and their mode of action. Freshly isolated jejunal IEL and lamina propria lymphocytes (LPL), as well as IEL and LPL depleted of CD4(+), CD8(+) and T-cell receptor (TCR)-γδ(+) cells were used as effector cells in anti-CD3-mediated redirected cytotoxicity against a murine FcγR-expressing cell line. Effector cell frequencies were estimated by effector to target cell titration and limiting dilution. The capacity of IEL and LPL to kill a Fas-expressing human T-cell line was also analysed. T-cell subsets were analysed for perforin, granzyme B, Fas-ligand (FasL), tumour necrosis factor-α (TNF-α) and TNF-related apoptosis inducing ligand (TRAIL) mRNA expression by reverse transcription–polymerase chain reaction (RT-PCR). Frequencies of IEL expressing the perforin and FasL proteins were determined by immunomorphometry. Both IEL and LPL exhibited significant Ca(2+)-dependent, anti-CD3-mediated cytotoxicity, ≈ 30% specific lysis at the effector to target cell ratio 100. The cytotoxic cells constituted, however, only a small fraction of IEL and LPL (≈ 0·01%). CD8(+) TCR-αβ(+) cells accounted for virtually all the cytotoxicity and expressed mRNA for all five cytotoxic proteins. The frequency of granzyme B-expressing samples was higher in CD8(+) cells than in CD4(+) cells (P<0·05 and <0·01 for IEL and LPL, respectively). In addition, both IEL and LPL exhibited significant spontaneous anti-CD3-independent cytotoxicity against Fas-expressing human T cells. This killing was mediated by Fas–FasL interaction. On average, 2–3% of the IEL expressed perforin and FasL. We speculate that CD8(+) memory cells accumulate in the jejunal mucosa and that the CD8(+) TCR-αβ(+) lymphocytes executing TCR/CD3-mediated, Ca(2+)-dependent cytotoxicity are classical cytotoxic T lymphocytes ‘caught in the act’ of eliminating infected epithelial cells through perforin/granzyme exocytosis. The observed Fas/FasL-mediated cytotoxicity may be a reflection of ongoing down-regulation of local immune responses by ‘activation-induced cell death’
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