Transcriptional targeting of B cells for induction of peripheral CD8 T cell tolerance.
Several mechanisms are in place to neutralize autoimmune CD8 T cells by tolerance induction. Developing self-specific CD8 T cells are eliminated in the thymus by Ag-presenting epithelial and dendritic cells (DCs). However, CD8 T cells escaping thymic central tolerance can also be inactivated by tolerance mechanisms in peripheral organs. In contrast to DCs, the role of B cells in generating CD8 T cell tolerance is not well-characterized. To investigate this question in more detail, we transcriptionally targeted Ag to B cells using B cell-specific retroviral vectors in vivo. Although Ag expression could be detected in B cells of thymus, lymph nodes, and spleen, B cells were unable to induce central tolerance of CD8 thymocytes. In contrast, in peripheral organs, we could identify clonal deletion and functional inhibition (anergy) of CD8 T cells as tolerance-inducing mechanisms. Although Ag expressed by B cells was acquired and cross-presented by DCs, B cells were also sufficient to tolerize CD8 T cells directly. These findings suggest exploitation of B cells for Ag-specific immunotherapy of CD8 T cell-mediated autoimmune diseases.
Werner-Klein
Melanie
M
Institute for Immunology, Ludwig-Maximilians-University, Goethestrasse 31, D-80336 Munich, Germany.
Dresch
Christiane
C
Marconi
Peggy
P
Brocker
Thomas
T
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells; D018941:Antigens, CD19 / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000235:genetics; D013950:Thymus Gland / Q000276:immunology; D014158:Transcription, Genetic
D018941:Antigens, CD19; D010047:Ovalbumin