High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors.
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.
Walter
Steffen
S
Department of Immunology, Institute for Cell Biology, Eberhard Karls University, Tübingen, Germany.
Bioley
Gilles
G
Bühring
Hans-Jörg
HJ
Koch
Sven
S
Wernet
Dorothee
D
Zippelius
Alfred
A
Pawelec
Graham
G
Romero
Pedro
P
Stevanović
Stefan
S
Rammensee
Hans-Georg
HG
Gouttefangeas
Cécile
C
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
D015789:HLA-A2 Antigen; D007633:Keratins