Interleukin-10 is crucial for maintenance but not for developmental induction of peripheral T cell tolerance.
To asses the requirement of interleukin (IL)-10 for peripheral CD4 T cell tolerance, the IL-10 knockout (KO) was introduced into a T cell receptor-transgenic mouse model (TCR1) specific for SV40 T antigen (Tag). IL-10-deficient TCR1-transgenic mice failed to establish antigen-specific T cell tolerance following sequential injections with Tag peptide. Nevertheless, IL-10 was not required for the establishment of CD4 T cell tolerance in double transgenic RT2/TCR1 mice in which Tag is expressed endogenously under control of the insulin promoter. However, in contrast to stable anergy in wild-type RT2/TCR1 mice, tolerant T cells in RT2/TCR1/Il-10KO mice could be driven into vigorous proliferation by exogenous antigenic stimulation in vivo. The observed reactivation of anergic T cell populations in IL-10-deficient mice was only seen after in vivo but not in vitro peptide priming, reflecting an important regulatory function of IL-10 in the context of the living organism. Taken together, these results demonstrate that IL-10 is required to maintain T cell tolerance following exposure to enhanced antigenic stimuli but is not essential for the induction of self-tolerance.
Seewaldt
Sonja
S
Institute for Medical Microbiology, Immunology and Hygiene and Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
Alferink
Judith
J
Förster
Irmgard
I
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017635:Clonal Anergy; D019672:Genes, T-Cell Receptor; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming; D016753:Interleukin-10