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Fine-tuning immune surveillance by fever-range thermal stress

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Abstract

An effectively orchestrated immune response to infection and disease depends on efficient trafficking of lymphocytes across vascular beds at distinct tissue sites. Local inflammation and systemic fever increase immune surveillance to immune-relevant sites throughout the body. During the initiation phase of inflammation, this tightly regulated process improves leukocyte trafficking to the secondary lymphoid organs where they undergo activation and expansion in response to cognate antigen. In the resolution phase following the clearance of the invading pathogen, lymphocyte entry is rapidly returned to baseline conditions. Specialized blood vessels termed high endothelial venules (HEVs) have emerged as critical ‘hotspots’ controlling the rate of lymphocyte entry into lymphoid organs during both phases of inflammation. In this review, we will examine the remarkably tight regulation of lymphocyte trafficking across HEVs conferred by inflammatory cues associated with the thermal element of fever. These studies have revealed a novel role for interleukin-6 (IL-6) trans-signaling in eliciting systemic effects on lymphocyte trafficking patterns to fine-tune immune surveillance.

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Acknowledgments

The authors would like to acknowledge Dr. Michelle M. Appenheimer, Dr. Qing Chen, and Dr. Wan-Chao Wang for seminal contributions to the work on fever-range thermal stress and to M.M.A. for review of the manuscript. This work was supported by grants from the NIH (CA79765, CA094045 and AI082039) and the Roswell Park Alliance Foundation.

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  1. Department of Immunology, Roswell Park Cancer Institute, Carlton & Elm Streets, Buffalo, NY, 14263, USA

    Daniel T. Fisher, Trupti D. Vardam, Jason B. Muhitch & Sharon S. Evans

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  1. Daniel T. Fisher
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  2. Trupti D. Vardam
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  3. Jason B. Muhitch
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  4. Sharon S. Evans
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Correspondence to Sharon S. Evans.

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Daniel T. Fisher and Trupti D. Vardam contributed equally to this work.

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Fisher, D.T., Vardam, T.D., Muhitch, J.B. et al. Fine-tuning immune surveillance by fever-range thermal stress. Immunol Res 46, 177–188 (2010). https://doi.org/10.1007/s12026-009-8122-9

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