Abstract

T-cell characteristics are dynamic and influenced by multiple factors. To test whether cells and the environment in the central nervous system (CNS) can influence T-cells, we tested if culturing mouse CD4+ T-cells on mouse primary astrocytes, compared with standard feeder cells, modified T-cell polarization to Th1 and Treg subtypes. Astrocytes supported the production of Th1 cells and Tregs, which was diminished by inflammatory activation of astrocytes, and glutamate accumulation that may result from impaired glutamate uptake by astrocytes strongly promoted Th1 production. These results demonstrate that astrocytes and the environment in the CNS have the capacity to regulate T-cell characteristics.

Highlights

  • There has been a rapidly increasing recognition that extensive interactions occur between the immune and nervous systems [1,2]

  • These results demonstrate that astrocytes can be potent inducers of Th1 cell production, and that the effects of astrocytes are additive to the effect of IL-12 on promoting Th1 cell differentiation

  • To begin to test if astrocytes can modify T cell characteristics, we used the straightforward paradigm of testing in vitro if astrocytes are capable of influencing the development of CD4+ T cells to different subtypes

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Summary

Introduction

There has been a rapidly increasing recognition that extensive interactions occur between the immune and nervous systems [1,2]. This progress is revising previous dogmas about the insular actions of these two systems, revealing instead that there are often bidirectional immune-neural interactions. Well-established are the detrimental actions of T cells in certain CNS diseases, such as being major drivers of the onset and progression of multiple sclerosis [12,13]. The two major populations of effector T helper (Th) cells present in the CNS of mice that are thought to contribute to EAE are interferon-c (IFNc)-producing Th1 cells and interleukin-17A (IL-17A)-producing Th17 cells. Recent discoveries that T cell subtype characteristics can be dynamic [21,22] have added a layer of complexity and indicates that environmental influences are capable of modulating the subtype characteristics of T cells

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