title: High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors.
abstract: Combining cell surface phenotyping with functional analysis, human CD8+ T cells have been divided into several subsets which are being studied extensively in diverse physiological situations, such as viral infection, cancer and ageing. In particular, so-called terminally differentiated effector cells possess a CD45RA+ CCR7- CD27- CD28- phenotype, contain perforin and, in different models, have been shown to exert direct ex vivo killing and to release interleukins upon both antigen-nonspecific and -specific stimulation. Using HLA class I multimers, we have identified a high frequency of peripheral CD8+ T cells that recognize a peptide derived from the self protein cytokeratin 18 presented by the HLA-A*0201 molecule. These cells can be detected in approximately 15% of the HLA-A2-positive healthy donors tested. A detailed analysis revealed that they must have divided extensively in vivo, have an effector cell phenotype and express various natural killer cell-associated receptors. Interestingly, however, they remained unresponsive to antigen-specific stimulation in vitro in terms of cytotoxicity and cytokine secretion. Thus, cytokeratin 18-specific cells constitute a frequently encountered, new CD8+ T lymphocyte subpopulation without classical effector status and with so far unknown function.
authors.affiliation: Department of Immunology, Institute for Cell Biology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Walter
authors.forename: Gilles
authors.initials: G
authors.lastname: Bioley
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.forename: Sven
authors.initials: S
authors.lastname: Koch
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wernet
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Cécile
authors.initials: C
authors.lastname: Gouttefangeas
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007633:Keratins / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015789:HLA-A2 Antigen; D007633:Keratins