T helper cell unresponsiveness: rapid induction in antigen-transgenic and reversion in non-transgenic mice.
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.
Bachmann
M F
MF
Department of Pathology, Institute of Immunology, Zürich, Switzerland.
Rohrer
U H
UH
Steinhoff
U
U
Bürki
K
K
Skuntz
S
S
Arnheiter
H
H
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D007108:Immune Tolerance; D007116:Immunization, Passive; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D017931:DNA Primers; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins