The pool of beta cell-specific CD8 + T-cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell “multipotency index” and found that beta cell-specific CD8 + T-cells retained a stem-like epigenetic multipotency score. Single cell ATAC-seq analysis confirmed the co-existence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8 + T-cells. Assessment of beta cell-specific CD8 + T-cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8 + T-cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8 + T cell responses, and document the utility of this novel methylation-based multipotency index for investigating human and mouse CD8 + T-cell differentiation.
Access to this document was granted through an Emerald subscription provided by emeraldsrm:198285 [] For AuthorsIf you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -The purpose of this paper is to empirically assess the link between worker loyalty and expected rewards, with special attention to reward desirability. Design/methodology/approach -Using employee-employer matched data collected from over 10,880 employees in nearly 670 workplaces in six culturally and economically diverse former socialist countries, the authors investigate the link between worker loyalty and expected rewards, taking into account reward desirability. Worker loyalty is measured using a composite of four variables related to participant's commitment to staying at his/her organization. The authors employ both OLS and fractional logit regression analysis, clustering at the firm level, and restricting the pooled sample to include only those participants who responded to all questions used in this analysis. In the basic model, the authors include expected rewards, with an extensive set of worker and workplace controls; in the extended model, the authors add reward desirability and the corresponding interaction variables. Findings -Using pooled data, the authors find that loyalty is positively correlated with expected rewards, and most strongly linked to the intrinsic reward chance to accomplish something worthwhile. When reward desirability is taken into account, consequences of unmet expectations emerge, and the relative importance of respectful and friendly co-workers diminishes. Neither generational nor lifecycle differences in loyalty are evident. Research limitations/implications -Due to financial constraints, country samples included in the pooled data are not nationally representative; nor are workplace samples representative. Personal contacts of local project coordinators and the snowballing technique used to expand the number of participating workplaces, as well as the requirement that participants be able to read the survey instrument, may contribute to selection bias. As such, the findings should be viewed as taking a preliminary or exploratory step toward developing a more global perspective of factors influencing worker loyalty and ...
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