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Journal of Virology, September 2001, p. 7803-7810, Vol. 75, No. 17
Institute for Immunology, University of Munich, 80336 Munich,1 and Department of Medicine II,
Klinikum Grosshadern, University of Munich, 81377 Munich,2 Germany, and Laboratory of Cell
Biology and Histology, University of Amsterdam, Amsterdam, The
Netherlands3
Received 12 January 2001/Accepted 24 May 2001
CD4+ T cells play a major role in the host defense
against viruses and intracellular microbes. During the natural course
of such an infection, specific CD4+ T cells are exposed to
a wide range of antigen concentrations depending on the body
compartment and the stage of disease. While epitope variants trigger
only subsets of T-cell effector functions, the response of
virus-specific CD4+ T cells to various concentrations of
the wild-type antigen has not been systematically studied. We
stimulated hepatitis B virus core- and hepatitis C virus NS3-specific
CD4+ T-cell clones which had been isolated from patients
with acute hepatitis during viral clearance with a wide range of
specific antigen concentrations and determined the phenotypic changes
and the induction of T-cell effector functions in relation to T-cell receptor internalization. A low antigen concentration induced the
expression of T-cell activation markers and adhesion molecules in
CD4+ T-cell clones in the absence of cytokine secretion and
proliferation. The expression of CD25, HLA-DR, CD69, and intercellular
cell adhesion molecule 1 increased as soon as T-cell receptor
internalization became detectable. A 30- to 100-fold-higher antigen
concentration, corresponding to the internalization of 20 to 30% of
T-cell receptor molecules, however, was required for the induction of
proliferation as well as for gamma interferon and interleukin-4
secretion. These data indicate that virus-specific CD4+ T
cells can respond to specific antigen in a graded manner depending on
the antigen concentration, which may have implications for a coordinate
regulation of specific CD4+ T-cell responses.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.7803-7810.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Different Levels of T-Cell Receptor Triggering
Induce Distinct Functions in Hepatitis B and Hepatitis C
Virus-Specific Human CD4+ T-Cell Clones
*
Corresponding author. Mailing address: Medizinische
Klinik II, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich,
Germany. Phone: 49-89-70 95 22 22. Fax: 49-89-70 00 95 40. E-mail:
helmut.diepolder{at}med2.med.uni-muenchen.de.
Journal of Virology, September 2001, p. 7803-7810, Vol. 75, No. 17
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.7803-7810.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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