| 1. |
- Rolf, Julia, 1979, et al.
(författare)
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Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets.
- 2008
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Ingår i: Molecular immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 45:9, s. 2607-20
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Tidskriftsartikel (refereegranskat)abstract
- CD1d-restricted natural killer T (NKT) cells can have multiple effects on an immune response, including the activation, regulation and attraction of innate immune cells, and modulation of adaptive immunity. Recent studies reveal that there are distinct subsets of NKT cells which selectively perform some of the functions attributed to CD1d-restricted cells, but the mechanisms underlying these functional differences have not been resolved. Our aim in this study was to identify novel NKT cell associated traits that would provide important insight into NKT cell activation and function. To this end, we have performed gene expression profiling of two separate subsets of NKT cells, analyzing genes differentially expressed in these cells compared to conventional CD4(+)NK1.1(-) T cells. We identify different sets of genes over expressed in each of the two NKT cell types, as well as genes that are common to the two CD1d-restricted NKT cell populations analyzed. A large number of these genes are highly relevant for NKT cell development, activation and function. Each NKT subtype displayed a unique set of chemokine receptors, integrins and molecules related to effector function, supporting the notion that distinct NKT cells can be selectively engaged and have diverse functions in different types of immune reactions.
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| 2. |
- Assarsson, Erika, et al.
(författare)
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Severe defect in thymic development in an insertional mutant mouse model.
- 2007
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 178:8, s. 5018-5027
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Tidskriftsartikel (refereegranskat)abstract
- Transgenic mice were generated expressing NK1.1, an NK cell-associated receptor, under control of the human CD2 promoter. Unexpectedly, one of the founder lines, Tg66, showed a marked defect in thymic development characterized by disorganized architecture and small size. Mapping of the transgene insertion by fluorescence in situ hybridization revealed integration in chromosome 2, band G. Already from postnatal day 3, the thymic architecture was disturbed with a preferential loss of cortical thymic epithelial cells, a feature that became more pronounced over time. Compared with wild-type mice, total thymic cell numbers decreased dramatically between 10 and 20 days of age. Thymocytes isolated from adult Tg66 mice were predominantly immature double-negative cells, indicating a block in thymic development at an early stage of differentiation. Consequently, Tg66 mice had reduced numbers of peripheral CD4(+) and CD8(+) T cells. Bone marrow from Tg66 mice readily reconstituted thymi of irradiated wild-type as well as RAG-deficient mice. This indicates that the primary defect in Tg66 mice resided in nonhemopoietic stromal cells of the thymus. The phenotype is observed in mice heterozygous for the insertion and does not resemble any known mutations affecting thymic development. Preliminary studies in mice homozygous for transgene insertion reveal a more accelerated and pronounced phenotype suggesting a semidominant effect. The Tg66 mice may serve as a useful model to identify genes regulating thymic epithelial cell differentiation, thymic development, and function.
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| 3. |
- Berntman, Emma
(författare)
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Immuno-modulatory functions of CD1d-restricted natural killer T cells
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focuses on a small population of non-conventional T lymphocytes, called natural killer T (NKT) cells. NKT cells have many unique features; such as recognition of glycolipids presented by CD1d, expression of NK receptors and rapid production of large amounts of cytokines, such as IL-4 and IFN-gamma,?upon activation. This early and robust cytokine burst is believed to give NKT cells the capacity to act as a link between innate and adaptive immunity. NKT cells are involved in a cohort of diverse immunological situations, including immune responses to tumors, pathogens, and autoimmunity, where both protective and detrimental roles have been described. In order to learn more about what genes are important for the characteristic features of NKT cells in general and for NKT cell subset in particular, we performed microarray experiments, thus studying the expression of all genes in two distinct NKT cell subsets compared to a control T cell population. We defined a gene expression profile shared by NKT cells, as well as gene profiles that were unique to the individual subsets. The common NKT cell gene expression profile suggested that NKT cells were predetermined for performing inflammatory and cytotoxic actions in non-lymphoid tissues such as gut and lung, while sharing many similarities with NK cells in activation and function. The subset unique gene profiles implied that while one subset appeared to be firmly associated with Th1-type reactions, the other subset had an enhanced potential for cytotox and for inducing Th2-associated immune responses. The NKT cells involvement in inflammatory mediation was confirmed in our last study where we showed that NKT cells were activated and potently produced IFN-gamma during the early phase of Salmonella-infection. Additionally, the infection was observed to skew the cytokine production profile of the NKT cells toward a protective IFN-gamma-dominated profile.
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| 4. |
- Berntman, Emma, et al.
(författare)
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The role of CD1d-restricted NK T lymphocytes in the immune response to oral infection with Salmonella typhimurium.
- 2005
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Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 35:7, s. 2100-2109
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Tidskriftsartikel (refereegranskat)abstract
- CD1d-restricted natural killer T (NKT) cells belong to the innate-like lymphocytes which respond rapidly to stress and infectious challenge. We have studied murine CD1d-restricted NKT cells in the early immune response to virulent Salmonella enterica serovar Typhimurium after oral infection. In the liver and spleen, neutrophil and macrophage numbers had increased several-fold by day 5 post-infection, while the frequency of B and T lymphocytes decreased. These cellular changes occurred independently of CD1d-restricted NKT cells, and further, CD1d-restricted T cells did not influence the bacterial load. However, in CD1d+ mice NK1.1+ T cells and invariant CD1d-restricted T cells were activated by the infection, as demonstrated by an increase in size, up-regulation of CD69 and production of IFN-. The NK1.1 antigen was down-modulated on these cells during the course of infection, while TCR levels were unaffected. While dendritic cells (DC) up-regulated CD1d-levels upon 24 h of in vitro exposure to the bacteria, increased CD1d expression was not evident on DC in vivo during infection. Furthermore, in vitro re-stimulation of CD1d-restricted T cells isolated from infected mice demonstrated a significant skewing of the cytokine profile, with suppressed IL-4 and increased IFN- production.
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| 5. |
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| 6. |
- Rolf, Julia, et al.
(författare)
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The enlarged population of marginal zone/CD1d(high) B lymphocytes in nonobese diabetic mice maps to diabetes susceptibility region Idd11.
- 2005
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 174:8, s. 4821-4827
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Tidskriftsartikel (refereegranskat)abstract
- The NOD mouse is an important experimental model for human type 1 diabetes. T cells are central to NOD pathogenesis, and their function in the autoimmune process of diabetes has been well studied. In contrast, although recognized as important players in disease induction, the role of B cells is not clearly understood. In this study we characterize different subpopulations of B cells and demonstrate that marginal zone (MZ) B cells are expanded 2- to 3-fold in NOD mice compared with nondiabetic C57BL/6 (B6) mice. The NOD MZ B cells displayed a normal surface marker profile and localized to the MZ region in the NOD spleen. Moreover, the MZ B cell population developed early during the ontogeny of NOD mice. By 3 wk of age, around the time when autoreactive T cells are first activated, a significant MZ B cell population of adult phenotype was found in NOD, but not B6, mice. Using an F2(B6 x NOD) cross in a genome-wide scan, we map the control of this trait to a region on chromosome 4 (logarithm of odds score, 4.4) which includes the Idd11 and Idd9 diabetes susceptibility loci, supporting the hypothesis that this B cell trait is related to the development of diabetes in the NOD mouse.
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