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Memory T Cells in the Chronic Inflammatory Microenvironment of Nasal Polyposis are Hyporesponsive to Signaling Through the T Cell Receptor

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Abstract

A majority of T cells from chronic inflammatory tissues derived from patients with nasal polyposis were found to express an effector memory phenotype. We report here that these memory T cells failed to activate NF-κB in response to TCR stimulation but responded normally when the proximal TCR signaling molecules were bypassed with PMA and ionomycin. The dysfunction of these cells was associated with a decrease in the phosphorylation of several TCR proximal signaling molecules including ZAP70, Lck and SLP-76. In addition to the disruption in the TCR signaling pathway, the nasal polyp-associated T cells were shown to have a defect in their ability to translocate LAMP-1 to the cell surface. The results presented here establish that the phenotype and anergy of the T cells in the nasal polyp are similar to those which is seen in memory T cells derived from human tumors and other sites of chronic inflammation.

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Acknowledgments

We would like to thank Dr. Wade J. Sigurdson for his expertise with the confocal microscope as well as Jenni L. Loyall and Liza Pope for their technical assistance. We thank Dr. Stephen Brooks for his helpful discussion of this work and Dr. Paul Wallace for his expert advice. We would also like to thank Thaddeus C. George of Amnis Corporation, and Dr. Hans Minderman and Kieran O'Loughlin of Roswell Park Cancer Institute for their expertise and assistance in ImageStream acquisition and analysis. This work was supported in part by the National Institute of Health Grant R56AI079188, RO1-CA108970 and RO1-CA131407, and by the Ralph Hochstetter Medical Research Fund in honor of Dr. Henry C. and Bertha H. Buswell (HKL).

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  1. Michelle R. Simpson-Abelson

    Present address: Department of Immunology, University of Pittsburgh, S708 BST South, Pittsburgh, PA, 15261, USA

Authors and Affiliations

  1. Department of Pediatrics, University at Buffalo School of Medicine and Biomedical Sciences, 239 Bryant St., 2nd Floor, Buffalo, NY, 14222, USA

    Heather K. Lehman

  2. Department of Microbiology and Immunology, University at Buffalo School at Medicine and Biomedical Sciences, 138 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA

    Michelle R. Simpson-Abelson, Thomas F. Conway Jr., Raymond J. Kelleher Jr. & Richard B. Bankert

  3. Department of Otolaryngology, University at Buffalo School of Medicine and Biomedical Sciences, 3435 Main Street, Buffalo, NY, 14214, USA

    Joel M. Bernstein

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  1. Heather K. Lehman
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Correspondence to Richard B. Bankert.

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Lehman, H.K., Simpson-Abelson, M.R., Conway, T.F. et al. Memory T Cells in the Chronic Inflammatory Microenvironment of Nasal Polyposis are Hyporesponsive to Signaling Through the T Cell Receptor. JARO 13, 423–435 (2012). https://doi.org/10.1007/s10162-012-0313-8

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