The Establishment And Mechanism Of Ovalbumin Immune Tolerance In DO11.10 Mice

The great task of distinguishing between potentially harmful entities bearing countless antigenic determinants and multiple self proteins is a complex process referred to as"immune tolerance"that begins in the thymus and continues in the peripheral lymphoid system. The principal mechanisms of peripheral tolerance are anergy (function unresponsiveness), deletion (apoptotic cell death), and suppression by regulatory T cells (Treg). Establishment and breakdown of peripheral immune tolerance has close relation with autoimmune disease (eg. multiple sclerosis, systemic lupus erythematosus, type 1 diabetes), graft-rejection, cancers and some of virus diseases, which require more sophisticated understanding of the mechanisms of peripheral tolerance. Consequently, studies of establishment and mechanism of non-self antigen-specific immune tolerance have both theoretical and practical implications for biology and medicine.OVA TCR transgenic mice on the BALB/c background, clone DO11.10, which express the Vα13/Vβ8.2 TCR on 55-65% of peripheral CD4~+T cells. Mucosal tolerance can be induced in DO11.10 mice by gavage or spontaneous ingestion of dietary ovalbumin antigen. However, little is known about the establishment and mechanism of OVA immune tolerance in DO11.10 mice with low-dose OVA intravenous injections. Here we showed that:1. Experimental group was injected i.v. 5μg OVA per mouse, which given three times at 5 days intervals. 3 days and 12 days later, experimental group/PBS control group were challenged. For OVA stimulated, experimental group lymphocytes specific proliferation can be suppressed significantly compared with control group, and the stimulation index of experimental group in DO11.10 mice was higher than the same group SI in BALB/c mice. The percentages of CD4~+CD25~+T cell subpopulation from experimental group were raised significantly compared with that of PBS control group. The percentage change in DO11.10 mice was greater than the percentage change in BALB/c mice. In conclusion, OVA antigen-specific peripheral tolerance has been successfully induced in DO11.10 mice.2. For CD4~+T cells epitope peptide stimulated, experimental group lymphocytes specific proliferation can be suppressed significantly compared with control group. For CTL epitope peptide stimulated, there was no significant difference between experimental and control group. The production of activated TGF-β1 was also showed remarkable increase compared with that of control group. However, the production of IL-10 was no obvious difference between experimental and control group. In conclusion, the establishment of OVA immune tolerance was induced by CD4+T cell suppression/anergy, which was dependent on TGF-βbut not IL-10.