Eomesodermin driven IL-10 production in effector CD8+ T cells promotes a memory phenotype.

CD8+ T cell differentiation is controlled by the transcription factors T-bet and Eomesodermin, in concert with the cytokines IL-2, IL-10 and IL-12. Among these pathways, the mechanisms by which T-box proteins and IL-10 interact to promote a memory T cell fate remain poorly understood. Here, we show that Eomes and IL-10 drive a central memory phenotype in murine CD8+ T cells. Eomes expression led to increased IL-10 expression by the effector CD8+ T cells themselves as well as an increase in the level of the lymph node homing selectin CD62L. Furthermore, exposure of effector CD8+ T cells to IL-10 maintained CD62L expression levels in culture. Thus, Eomes promotes a step-wise transition of effector T cells towards a memory phenotype, synergizing with IL-10 to enhance the expression of CD62L. The early augmentation of lymph node homing markers by Eomes may facilitate the retention of effector T cells in the relatively low inflammatory milieu of the secondary lymphoid organs that promotes central memory development.

Eomesodermin Increases Survival and IL-2 Responsiveness of Tumor-specific CD8+ T Cells in an Adoptive Transfer Model of Cancer Immunotherapy.

Tumor-specific CD8 T cells often fail to elicit effective antitumor immune responses due to an inability to expand into a substantial effector population and persist long-term in vivo. Using an adoptive transfer model of cancer immunotherapy, we demonstrate that constitutive eomesodermin (Eomes) expression in tumor-specific CD8 T cells improves tumor rejection and survival. The increase in tumor rejection was associated with an increased number and persistence of CD8 T cells in lymphoid tissues during acute tumor rejection, tumor regrowth, and in mice that remained tumor-free. Constitutive Eomes expression increased expression of CD25, and this was associated with enhanced interleukin-2 responsiveness and tumor-specific CD8 T-cell proliferation. Moreover, constitutive Eomes expression improved cell survival. Taken together, our data suggest that constitutive Eomes expression enhances CD8 T-cell proliferation and survival, in part through the enhancement of interleukin-2 responsiveness through CD25 induction.

Effector, Memory, and Dysfunctional CD8(+) T Cell Fates in the Antitumor Immune Response.

The adaptive immune system plays a pivotal role in the host's ability to mount an effective, antigen-specific immune response against tumors. CD8(+) tumor-infiltrating lymphocytes (TILs) mediate tumor rejection through recognition of tumor antigens and direct killing of transformed cells. In growing tumors, TILs are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment. These interactions and signals can lead to transcriptional, functional, and phenotypic changes in TILs that diminish the host's ability to eradicate the tumor. In addition to effector and memory CD8(+) T cells, populations described as exhausted, anergic, senescent, and regulatory CD8(+) T cells have been observed in clinical and basic studies of antitumor immune responses. In the context of antitumor immunity, these CD8(+) T cell subsets remain poorly characterized in terms of fate-specific biomarkers and transcription factor profiles. Here we discuss the current characterization of CD8(+) T cell fates in antitumor immune responses and discuss recent insights into how signals in the tumor microenvironment influence TIL transcriptional networks to promote CD8(+) T cell dysfunction.

Speech recognition interface to a hospital information system using a self-designed visual basic program: initial experience.

Speech recognition (SR) in the radiology department setting is viewed as a method of decreasing overhead expenses by reducing or eliminating transcription services and improving care by reducing report turnaround times incurred by transcription backlogs. The purpose of this study was to show the ability to integrate off-the-shelf speech recognition software into a Hospital Information System in 3 types of military medical facilities using the Windows programming language Visual Basic 6.0 (Microsoft, Redmond, WA). Report turnaround times and costs were calculated for a medium-sized medical teaching facility, a medium-sized nonteaching facility, and a medical clinic. Results of speech recognition versus contract transcription services were assessed between July and December, 2000. In the teaching facility, 2042 reports were dictated on 2 computers equipped with the speech recognition program, saving a total of US dollars 3319 in transcription costs. Turnaround times were calculated for 4 first-year radiology residents in 4 imaging categories. Despite requiring 2 separate electronic signatures, we achieved an average reduction in turnaround time from 15.7 hours to 4.7 hours. In the nonteaching facility, 26600 reports were dictated with average turnaround time improving from 89 hours for transcription to 19 hours for speech recognition saving US dollars 45500 over the same 6 months. The medical clinic generated 5109 reports for a cost savings of US dollars 10650. Total cost to implement this speech recognition was approximately US dollars 3000 per workstation, mostly for hardware. It is possible to design and implement an affordable speech recognition system without a large-scale expensive commercial solution.