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Homing Properties (homing + property)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Getting to the crux of the matter: IL-23 and Th17 cell accumulation in the CNS

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009
Benjamin M. Segal
Abstract IL-23 plays a critical role in EAE induced by the active immunization of C57BL/6 mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein (MOG35,55). It was initially assumed that the pathogenic effects of IL-23 were directly related to the generation, expansion and/or stabilization of autoreactive CD4+ Th17 cells. However, a number of recent studies have uncovered discrepancies between the requirement for IL-23, as opposed to Th17 cells or their products (IL-17A, IL-17F and IL-22), in the development of EAE. In this issue of the European Journal of Immunology, it is demonstrated that impairment of IL-23 signaling does not impede the expansion of myelin-specific CD4+ T cells in peripheral lymphoid tissues but inhibits their accumulation in the CNS. This paper contributes to a growing body of data that implicates IL-23 in the acquisition of CNS homing properties by autoreactive effector cells. [source]

T cells developing in fetal thymus of T-cell receptor ,-chain transgenic mice colonize ,, T-cell-specific epithelial niches but lack long-term reconstituting potential

IMMUNOLOGY, Issue 1 2006
Karin Leandersson
Summary The ,, T cells generated during mouse fetal development are absolutely dependent on their invariant T-cell receptors (TCRs) for their function. However, there is little information on whether the epithelial homing properties of fetal T cells might also be developmentally induced by factors unrelated to TCR specificity. We have previously described TCR ,-chain transgenic (2B4 TCR-, TG) mice, in which the transgenic TCR ,-chain is expressed early, already at embryonic day 14 (E14). These mice have a large population of ,,, T-cell-like' CD4, CD8, (double-negative; DN) ,, T cells, some of which develop during E14,E18 contemporarily to intraepithelial lymphocytes (IELs) expressing invariant TCR-,,. Using the 2B4 TCR-, TG mouse model we have been able to more precisely study the impact of a variant TCR expression on IEL development and homing. In this study we show that TCR-, TG and TCR-, TG crossed to TCR-,-deficient mice (TCR-, TG × TCR-,,/,) carry TG TCR-,+ dendritic epidermal T cells (DETCs) and TCR-, TG+ IELs in the small intestine. The TG+ DETCs develop and seed the epidermis with similar kinetics as V,5+ DETCs of normal mice, in contrast to the TCR-,,+ DETCs found in TCR-,,/, mice. However, whereas the intestinal TCR-, TG+ IELs persist in old mice (> 20 months), the TCR-, TG+ DETCs do not. The data in this study indicate that the timing of TCR expression and thereby development during ontogeny regulates the specific homing potential for fetal T cells but not their subsequent functions and properties. [source]

Low-dose cyclosporine A therapy increases the regulatory T cell population in patients with atopic dermatitis

ALLERGY, Issue 11 2009
C. Brandt
Background:, Atopic dermatitis (AD) is a T cell dependent chronic relapsing inflammatory skin disorder successfully treated with cyclosporine A (CsA). Clinical observations indicate that even low-dose CsA therapy is successful in severely affected AD patients. We studied the impact of low-dose CsA therapy on the ability of T helper cells to be activated, and examined whether regulatory T (Treg) cells are increased in these patients. Methods:, Peripheral T cells were activated in a whole blood sample and interleukin-2 producing cells were measured by intracellular cytokine staining. Regulatory T cells were analyzed by intracellular FoxP3 staining. Regulatory T cells (CD4+CD25+CD127low) and effector T cells (CD4+CD25,CD127+) were sorted by flow cytometry and used for suppression assays. Results:, A group of AD patients treated with low-dose CsA had a significantly larger Treg cell population than a healthy control subject group. In individual patients, onset of low-dose CsA therapy reduced the ability of T cells to be activated to 42 ± 18% (P < 0.005) and significantly increased Treg cells, both in absolute numbers (1.6-fold change) and frequencies (1.7-fold change). Treg cells from AD patients showed similar suppressive capacities as Treg cells from healthy donors. Furthermore, Treg cells from AD patients had skin homing properties. Conclusion:, Our results indicate that the therapeutic effect of low-dose CsA therapy in AD patients might be not only mediated by the inhibition of T cell hyperactivity but also by an increased population of Treg cells. [source]

Generation of stable retrovirus packaging cell lines after transduction with herpes simplex virus hybrid amplicon vectors,

THE JOURNAL OF GENE MEDICINE, Issue 3 2002
Miguel Sena-Esteves
Abstract Background A number of properties have relegated the use of Moloney murine leukemia virus (Mo-MLV)-based retrovirus vectors primarily to ex vivo protocols. Direct implantation of retrovirus producer cells can bypass some of the limitations, and in situ vector production may result in a large number of gene transfer events. However, the fibroblast nature of most retrovirus packaging cells does not provide for an effective distribution of vector producing foci in vivo, especially in the brain. Effective development of new retrovirus producer cells with enhanced biologic properties may require the testing of a large number of different cell types, and a quick and efficient method to generate them is needed. Methods Moloney murine leukemia virus (Mo-MLV) gag-pol and env genes and retrovirus vector sequences carrying lacZ were cloned into different minimal HSV/AAV hybrid amplicons. Helper virus-free amplicon vectors were used to co-infect glioma cells in culture. Titers and stability of retrovirus vector production were assessed. Results Simultaneous infection of two glioma lines, Gli-36 (human) and J3T (dog), with both types of amplicon vectors, generated stable packaging populations that produced retrovirus titers of 0.5,1.2×105 and 3.1,7.1×103 tu/ml, respectively. Alternatively, when cells were first infected with retrovirus vectors followed by infection with HyRMOVAmpho amplicon vector, stable retrovirus packaging populations were obtained from Gli-36 and J3T cells producing retrovirus titers comparable to those obtained with a traditional retrovirus packaging cell line, ,CRIPlacZ. Conclusions This amplicon vector system should facilitate generation of new types of retrovirus producer cells. Conversion of cells with migratory or tumor/tissue homing properties could result in expansion of the spatial distribution or targeting capacity, respectively, of gene delivery by retrovirus vectors in vivo. Copyright © 2002 John Wiley & Sons, Ltd. [source]