Faculty Collaboration Database

Sinonasal T-cell expression of cytotoxic mediators granzyme B and perforin is reduced in patients with chronic rhinosinusitis. Am J Rhinol Allergy 2017 Nov 01;31(6):352-356

Date

11/11/2017

Pubmed ID

29122079

Pubmed Central ID

PMC5691237

DOI

10.2500/ajra.2017.31.4474

Scopus ID

2-s2.0-85035054256 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

BACKGROUND: CD8+ T cells and natural killer (NK) cells are cytotoxic cells that use granzyme B (GrB) and perforin. Defective cytotoxic function is known to play a role in dysregulated immune response as seen in chronic sinusitis, also referred to as chronic rhinosinusitis (CRS). However, to our knowledge, in the United States, neither GrB or perforin expression has been reported in patients with CRS.

OBJECTIVE: The aim of this study was to investigate sinonasal cytotoxic cells, their mediators, and cell-specific distribution of these mediators in patients with CRS with nasal polyp (CRSwNP) and in patients with CRS without nasal polyp (CRSsNP).

METHODS: Blood and sinus tissue samples were taken from patients with CRSsNP (n = 8) and CRSwNP (n = 8) at the time of surgery. Control subjects (n = 8) underwent surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. The cells were analyzed via flow cytometry by using CD8 expression to identify cytotoxic T cells and CD56 expression to identify NK cells. Intracellular GrB and perforin expression were analyzed with flow cytometry.

RESULTS: We observed no significant differences in plasma or peripheral blood immune cell numbers or specific levels of GrB or perforin among the groups. In the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP, there was a significant decrease in GrB and perforin levels (p < 0.05) despite similar or increased numbers of cytotoxic cells when compared with the controls. The overall decrease in GrB and perforin in the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP was due to decreased T cell production. There was no difference in total NK cell count or expression of perforin or GrB among all the groups.

CONCLUSION: Total levels of sinonasal GrB and perforin were decreased in the sinonasal mucosa of both the patients with CRSwNP and the patients with CRSsNP compared with the controls, whereas sinonasal CD8+ T cells, (but not NK cells,), intracellular stores of GrB and perforin were reduced in the patients with CRSwNP compared with the controls.

Author List

Smith SE, Schlosser RJ, Yawn JR, Mattos JL, Soler ZM, Mulligan JK

Author

James Roy Yawn MD Assistant Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Chronic Disease
Female
Granzymes
Humans
Killer Cells, Natural
Male
Middle Aged
Paranasal Sinuses
Perforin
Rhinitis
Sinusitis
T-Lymphocytes