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T cell tolerance is usually established by clonal deletion of self-specific T cells in the thymus, or some times, in the periphery. Alternatively, tolerance may also be achieved by induction of clonal T cell unresponsiveness by a poorly understood mechanism called "anergy". We found that transgenic mice expressing a soluble form of vesicular stomatitis virus (VSV) glycoprotein (G) predominantly in liver and kidney exhibited normal B cell responses. VSV-G-specific T help-independent neutralizing IgM responses were within normal ranges, but no T help-dependent neutralizing IgG antibodies were generated upon immunization with recombinant VSV-G protein and recombinant vaccinia virus expressing VSV-G. This demonstrated absence of B cell tolerance but presence of T helper cell unresponsiveness. After adoptive transfer of transgenic spleen cells into thymectomized immuno-incompetent hosts, the unresponsive T helper cells regained function and switched the neutralizing IgM response to IgG, comparably to control T helper cells, within 7 days. Conversely, when naive non-transgenic spleen cells were transferred into transgenic mice, VSV-G-specific T helper cells became unresponsive within 3-4 days. These results suggest that VSV-G-specific T helper cells are rendered unresponsive within a few days in the VSV-G transgenic host also outside of the thymus and that this unresponsiveness was reversed by transfer into antigen-free recipients.

Original publication

DOI

10.1002/eji.1830241207

Type

Journal article

Journal

Eur J Immunol

Publication Date

12/1994

Volume

24

Pages

2966 - 2973

Keywords

Animals, B-Lymphocytes, Base Sequence, DNA Primers, Immune Tolerance, Immunization, Passive, Lymphocyte Cooperation, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, T-Lymphocytes, Helper-Inducer, Viral Envelope Proteins