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- Brenden, N., et al.
(författare)
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Differential MHC expression requirements for positive selection of separate TCR Vb families
- 1999
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Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 49:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6+CD4+ and Vb10+CD4+ thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13+CD8+ thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea→NOD-Ea chimeras have an increased positive selection of Vb13+CD8+ cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6+CD4+ cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10+CD4+ cells was restricted to E-expressing thymic epithelium only. For Vb13+CD8+ cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6+CD4+ cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10+CD4+ cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.
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| 2. |
- Brenden, N., et al.
(författare)
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Disease-protected major histocompatibility complex Ea-transgenic non- obese diabetic (NOD) mice show interleukin-4 production not seen in susceptible Ea-transgenic and non-transgenic NOD mice
- 1998
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 95:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- The non-obese diabetic (NOD) mouse is an animal model for insulin- dependent diabetes that has many similarities to the human disease. NOD mice transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes and rarely develop insulitis. An Ea transgene mutated in the promoter region, (ΔY) lacks E expression on most B cells, thymic medullary epithelium and primary antigen-presenting cells, and confers no protection whatsoever. We have used these transgenic NOD mice, together with non-transgenic NOD mice, to study the correlation of E expression and production of interleukin-4 (IL-4) and interferon-γ (IFN-γ). We show that protected E-transgenic NOD mice have elevated levels of IL-4 compared with non-transgenic mice, both in the thymus and in the periphery. However, susceptible ΔY-transgenic mice have elevated thymic IL-4 levels, but express almost as little IL-4 as non-transgenic NOD mice in the periphery. This drop in peripheral IL-4 production seen in ΔY-transgenic mice thus correlates with the decreased E expression in the periphery of ΔY-transgenic NOD mice. In contrast, there were no differences in IFN-γ production between the three NOD lines. We suggest that Ea-transgenic NOD mice have E-selected regulatory T cells producing IL-4, which are subsequently activated by E-expressing primary antigen-presenting cells in the periphery. This activation would then be instrumental for the E-mediated protection from disease in NOD mice. Such a process would explain the total absence of protection in ΔY-transgenic NOD mice, despite their widespread E expression.
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| 3. |
- Brenden, N., et al.
(författare)
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E expression is needed on both bone marrow derived cells and thymic epithelium to increase IL-4 production and achieve protection in NOD bone marrow chimeras
- 1999
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 11:10, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- The NOD mouse is an animal model for insulin-dependent diabetes with many similarities to the human disease. NOD mice which are transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes and rarely develop insulitis. We have constructed bone marrow chimeras between transgenic and non-transgenic NOD mice to study the correlation of E expression on bone marrow derived cells and thymic epithelium vs the production of IL-4 and IFN-γ. We show that NOD-E→NOD-E and NOD-E→NOD chimeras have elevated levels of IL-4 compared to NOD→NOD and NOD→NOD-E chimeras in the thymus. However, in the periphery the protected NOD-E→NOD-E show much higher IL-4 levels than any of the other chimeras. This drop in peripheral IL-4 production seen in NOD-E→NOD, NOD→NOD-E and NOD→NOD chimeras correlates with the increased insulitis seen in these mice compared to NOD-E→NOD-E. In contrast, there were no differences in IFN-γ production between the chimeras. We suggest that the precommitted, regulatory T cells, selected in an E-expressing thymic environment, need continuous interaction with E-expressing primary antigen presenting cells in the periphery for optimal IL-4 production. Decrease in IL-4 production correlates with increased insulitis.
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| 6. |
- Dornheim, Tobias, et al.
(författare)
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Ab initio density response and local field factor of warm dense hydrogen
- 2024
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Ingår i: Matter and Radiation at Extremes. - : AIP Publishing. - 2468-2047 .- 2468-080X. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- We present quasi-exact ab initio path integral Monte Carlo (PIMC) results for the partial static density responses and local field factors of hydrogen in the warm dense matter regime, from solid density conditions to the strongly compressed case. The full dynamic treatment of electrons and protons on the same footing allows us to rigorously quantify both electronic and ionic exchange-correlation effects in the system, and to compare the results with those of earlier incomplete models such as the archetypal uniform electron gas or electrons in a fixed ion snapshot potential that do not take into account the interplay between the two constituents. The full electronic density response is highly sensitive to electronic localization around the ions, and our results constitute unambiguous predictions for upcoming X-ray Thomson scattering experiments with hydrogen jets and fusion plasmas. All PIMC results are made freely available and can be used directly for a gamut of applications, including inertial confinement fusion calculations and the modeling of dense astrophysical objects. Moreover, they constitute invaluable benchmark data for approximate but computationally less demanding approaches such as density functional theory or PIMC within the fixed-node approximation.
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| 7. |
- Dornheim, Tobias, et al.
(författare)
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Ab initio path integral Monte Carlo simulations of warm dense two-component systems without fixed nodes: Structural properties
- 2024
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 160:16
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Tidskriftsartikel (refereegranskat)abstract
- We present extensive new ab initio path integral Monte Carlo (PIMC) results for a variety of structural properties of warm dense hydrogen and beryllium. To deal with the fermion sign problem—an exponential computational bottleneck due to the antisymmetry of the electronic thermal density matrix—we employ the recently proposed [Y. Xiong and H. Xiong, J. Chem. Phys. 157, 094112 (2022); T. Dornheim et al., J. Chem. Phys. 159, 164113 (2023)] ξ-extrapolation method and find excellent agreement with the exact direct PIMC reference data where available. This opens up the intriguing possibility of studying a gamut of properties of light elements and potentially material mixtures over a substantial part of the warm dense matter regime, with direct relevance for astrophysics, material science, and inertial confinement fusion research.
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| 8. |
- Dornheim, Tobias, et al.
(författare)
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Physical insights from imaginary-time density-density correlation functions
- 2023
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Ingår i: Matter and Radiation at Extremes. - : AIP Publishing. - 2468-2047 .- 2468-080X. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- An accurate theoretical description of the dynamic properties of correlated quantum many-body systems, such as the dynamic structure factor S(q, ω), is important in many fields. Unfortunately, highly accurate quantum Monte Carlo methods are usually restricted to the imaginary time domain, and the analytic continuation of the imaginary-time density-density correlation function F(q, τ) to real frequencies is a notoriously hard problem. Here, it is argued that often no such analytic continuation is required because by definition, F(q, τ) contains the same physical information as does S(q, ω), only represented unfamiliarly. Specifically, it is shown how one can directly extract key information such as the temperature or quasi-particle excitation energies from the τ domain, which is highly relevant for equation-of-state measurements of matter under extreme conditions [T. Dornheim et al., Nat. Commun. 13, 7911 (2022)]. As a practical example, ab initio path-integral Monte Carlo results for the uniform electron gas (UEG) are considered, and it is shown that even nontrivial processes such as the roton feature of the UEG at low density [T. Dornheim et al., Commun. Phys. 5, 304 (2022)] are manifested straightforwardly in F(q, τ). A comprehensive overview is given of various useful properties of F(q, τ) and how it relates to the usual dynamic structure factor. In fact, working directly in the τ domain is advantageous for many reasons and opens up multiple avenues for future applications.
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