Publication

Different levels of T-cell receptor triggering induce distinct functions in hepatitis B and hepatitis C virus-specific human CD4(+) T-cell clones

Journal Paper/Review - Sep 1, 2001

Units
PubMed

Citation
Diepolder H, Gruener N, Gerlach T, Jung M, Wierenga E, Pape G. Different levels of T-cell receptor triggering induce distinct functions in hepatitis B and hepatitis C virus-specific human CD4(+) T-cell clones. Journal of virology 2001; 75:7803-10.
Type
Journal Paper/Review (English)
Journal
Journal of virology 2001; 75
Publication Date
Sep 1, 2001
Issn Print
0022-538X
Pages
7803-10
Brief description/objective

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.