Abstract

The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model immune responses. The goals of this report are to 1) briefly summarize previous work revealing how DCs respond to various forms of physiological stress and 2) to present new data highlighting the potential for chronic mild cold stress inherent to mice housed at the required standard ambient temperatures to influence baseline DCs properties in naïve and tumor-bearing mice. As recent data from our group shows that CD8+ T cell function is significantly altered by chronic mild cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether housing temperature may also be influencing DC function. Here we report that there are several significant phenotypical and functional differences among DC subsets in naïve and tumor-bearing mice housed at either standard housing temperature or at a thermoneutral ambient temperature, which significantly reduces the extent of cold stress. The new data presented here strongly suggests that, by itself, the housing temperature of mice can affect fundamental properties and functions of DCs. Therefore differences in basal levels of stress due to housing should be taken into consideration when interpreting experiments designed to evaluate the impact of additional variables, including other stressors on DC function.

Highlights

  • Dendritic cells (DCs) play a vital role in the generation of effective and long-term immune protection from cancer and other diseases

  • DC function is dependent on the timing of antigen exposure and/or the type of antigen used, so these factors may affect the observed relationship between stress and DC function [44]

  • In addition to summarizing some of the existing data on the effects of various stressors and stress hormones on DC function, we show here that the numbers and percentages of different subsets of DCs can be dependent upon housing temperature

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Summary

Introduction

Dendritic cells (DCs) play a vital role in the generation of effective and long-term immune protection from cancer and other diseases. Considerable progress has been made toward understanding how DCs become tolerogenic [10, 14, 15], the precise mechanisms by which tumors modulate cross-priming to suppress the CD8+ T cell response remain largely unknown. This incomplete understanding of the role DCs play in immune evasion remains a vital question as DCs are being actively investigated in mouse models to help reveal their role in the anti-tumor immune response. It is important to fully recognize the impact of any inherent physiological factors in mice, which can alter DC function and to understand the impact these factors could have on experimental models of antigen presentation and immunotherapy

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