82 research outputs found
From non-Brahmin priests of the goddess to ascetics of god Mahima Alekha
Get PDFThis article deals with Mahima Dharma a contemporary vernacular ascetic religion of Odisha/Eastern India displaying a rich diversity in its regional configurations. In this paper the author proposes to look at the main protagonists of the religion, the ascetics (babas), as non-Brahmin priests, who have incorporated shakti, the power of local goddesses into their disciplined bodies and in doing so have transformed the feminine element of the Hindu belief into the belief of the indescribable and abstract god Alekha. Mahima Dharma is seen in this contribution as a sort of micro structure on the one hand of popular asceticism in rural India and on the other hand as a recent religious reform movement integrating local non-Brahmin priesthood and the local belief in goddesses into the mainstream of the male Hindu pantheon. This article draws on the author's PhD fieldwork research (1999-2002), published in 2002 as a monograph (Guzy 2002)
Provocative exhibits at the Seventeen Gallery
No full textTwo studies identify a tissue-autonomous innate immune mechanism whereby infection provokes epithelial cells to produce IL-17C that engages an epithelial receptor composed of IL-17RA and IL-17RE chains, which promotes host defense and immune activation
ZAP70 holds the key to kinetic proofreading for TCR ligand discrimination
Get PDFA key biochemical event that enables T cells to discriminate between TCR antigens of varying affinities and to respond only to high-affinity antigens is full activation of the kinase ZAP70
Purification of the T Cell Antigen Receptor and Analysis by Blue-Native PAGE
No full textThe T cell antigen receptor (TCR) is a multi-protein complex composed of six different transmembrane subunits, which form complexes of various sizes on the surface of resting T cells. The stoichiometry of the smallest form was recently determined to be αβγεδεζζ, whereas that of the larger forms is unknown. The roles of the different forms and their ratios are poorly defined. Biochemical analyses to address these questions must focus on the detergent and the best native conditions to maintain the integrity of the complexes. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) is a high-resolution native protein separation method that relies on the dye Coomassie blue to confer negative charge for separation. Using this powerful approach, the size, subunit composition and the relative abundance of the different TCR forms can be studied. We present here four methods to isolate the TCR in a native form and details to analyse it by BN-PAGE
Breast cancer stem cell-derived tumors escape from γδ T cell immunosurveillance in vivo by modulating γδ T cell ligands
No full textTriple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.ligand
Small intestinal epithelial cells from C57Bl/6J mice
No full textTotal proteome from sorted primary intestinal epithelial cells isolated from the small intestines of 4 C57Bl/6J mic
Intraepithelial T cells move from gut to breast to shape lactation
No full textDuring late gestation, unconventional intraepithelial αβ T cells migrate from the gut to the mammary gland to remodel the tissue for lactation and enhance its mucosal barrier state
Isolation, Characterization, and Culture of Intestinal Intraepithelial Lymphocytes
Get PDFIntestinal intraepithelial lymphocytes (IEL) comprise distinct groups of innate-like and memory T cells that collectively form one of the largest T cell compartments in the body. IEL are located within the intestinal epithelium and are the first immune cells in the gut to interact with the food, microbiota, and pathogens that the gut is continually exposed to. IEL can respond rapidly to external insults to protect the small intestinal epithelium but are also considered regulatory cells that are important to maintain the homeostasis of the gut. However, the mechanisms of IEL activation and their interactions within the epithelium remain largely elusive. Indeed, IEL are not commonly evaluated even in studies of gut immunology, potentially because they are perceived as being difficult to isolate and study. In this protocol, we present a simplified method to isolate IEL from the murine small intestine and provide representative data for flow cytometric analyses of the different IEL subsets. We also outline two procedures for culturing IEL, which can permit functional studies and coculture with epithelial cells. These strategies should make studies of this large but enigmatic T cell compartment more accessible and open up understanding of homeostatic mechanisms in the intestine, and tissue-associated immunity.</p
Mechanisms of activation of innate-like intraepithelial T lymphocytes
Get PDFIntraepithelial T lymphocytes (T-IEL) contain subsets of innate-like T cells that evoke innate and adaptive immune responses to provide rapid protection at epithelial barrier sites. In the intestine, T-IEL express variable T cell antigen receptors (TCR), with unknown antigen specificities. Intriguingly, they also express multiple inhibitory receptors, many of which are normally found on exhausted or antigen-experienced T cells. This pattern suggests that T-IEL are antigen-experienced, yet it is not clear where, and in what context, T-IEL encounter TCR ligands. We review recent evidence indicating TCR antigens for intestinal innate-like T-IEL are found on thymic or intestinal epithelium, driving agonist selection of T-IEL. We explore the contributions of the TCR and various co-stimulatory and co-inhibitory receptors in activating T-IEL effector functions. The balance between inhibitory and activating signals may be key to keeping these highly cytotoxic, rapidly activated cells in check, and key to harnessing their immune surveillance potential
Epithelial decision makers: in search of the 'epimmunome'
No full textFrequent microbial and nonmicrobial challenges to epithelial cells trigger discrete pathways, promoting molecular changes such as the secretion of specific cytokines and chemokines and alterations to molecules displayed at the epithelial cell surface. In combination, these molecules impose key decisions on innate and adaptive immune cells. Depending on context, those decisions can be as diverse as those imposed by professional antigen-presenting cells, benefiting the host by balancing immune competence with the avoidance of immunopathology. Nonetheless, this potency of epithelial cells is also consistent with the causal contribution of epithelial dysregulation to myriad inflammatory diseases. This pathogenic axis provides an attractive target for tissue-specific clinical manipulation. In this context, a research goal should be to identify all molecules used by epithelial cells to instruct immune cells. We term this the 'epimmunome'.</p
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