Memory T cells in the chronic inflammatory microenvironment of nasal polyposis are hyporesponsive to signaling through the T cell receptor.
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.
Department of Pediatrics, University at Buffalo School of Medicine and Biomedical Sciences, 239 Bryant St., 2nd Floor, Buffalo, NY 14222, USA.
Heather K
HK
Lehman
Michelle R
MR
Simpson-Abelson
Thomas F
TF
Conway
Raymond J
RJ
Kelleher
Joel M
JM
Bernstein
Richard B
RB
Bankert
D018106:CD28 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D061207:Calcium Ionophores; D016022:Case-Control Studies; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D015759:Ionomycin; D008213:Lymphocyte Activation; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D009298:Nasal Polyps / Q000276:immunology*; D010641:Phenotype; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D052118:Lysosomal-Associated Membrane Protein 1
D018106:CD28 Antigens; D017252:CD3 Complex; D061207:Calcium Ionophores; D015759:Ionomycin; D051907:Lysosomal Membrane Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1