Split tolerance to a viral antigen expressed in thymic epithelium and keratinocytes

When expressed as a transgene from the keratin 14 (K14) promoter in an MHC class II-deficient mouse, I-Ab expressed in thymic cortical epithelium promotes positive but not negative selection of I-Ab-restricted CD4(+) T cells (Laufer, T. M. et al., Nature 1996. 383:81-85). Transgenic mice expressing the E7 protein of human papilloma virus 16 from the K14 promoter were studied to determine the consequence of expression of a cytoplasmic/nuclear protein from the K14 promoter. K14E7-transgenic mice express E7 in the thymus and skin without evidence for autoimmunity to E7. Repeated immunization of FVB(H-2(q)) or F1(C57BV6JxFVB) mice with E7 elicited similar antibody responses to the defined B cell epitopes of E7 in K14E7-transgenic and non-transgenic animals. In contrast, for each genetic background, a single immunization with E7 elicited demonstrable T cell proliferative responses to the major promiscuous T helper epitope of E7 in the transgenic but not the non-transgenic animals. Further,E7-immunized non-transgenic F1 (FVBxC57BL/6J) animals developed strong E7-specific cytotoxic T lymphocyte (CTL) responses and were protected against challenge with E7(+) tumors, whereas similarly immunized K14E7-transgenic animals had a markedly reduced CTL response to E7 and no E7-specific tumor protection was observed, although the antibody and CTL response to ovalbumin was normal. Expression of E7 protein as a transgene from the K14 promoter in the skin and thymus thus induces E7-specific tolerance in the cytotoxic T effector repertoire, together with expansion of the E7-specific T helper repertoire. These findings demonstrate that limited tissue distribution of an autoantigen may result in split tolerance to that autoantigen.

The effects of work control and job demands on employee adjustment and work performance

The present study examined the effects of work control and job demands on employee adjustment and work performance using a multidimensional measure of work control (assessing levels of task control, decision control and work scheduling control). It was proposed that the negative effects of job demands and employee adjustment would be moderated by high levels of task control. It was also proposed that there would be evidence of main effects of both job demands and work control (particularly task-related levels of control) on employee adjustment. To test these predictions, a study of 135 university employees holding administrative positions was undertaken. Methodological improvements over previous research included the use of both self-reported adjustment measures and supervisor ratings of work performance as outcome variables, and the assessment of the predictor and outcome measures at different points in time (self-reported adjustment was assessed at both Times 1 and 2). The results revealed some support for the proposal that the effects of job demands would be buffered by high levels of task control, but not more peripheral aspects of work control. There were also significant main effects of task control on job satisfaction.