A new T-cell activation mode for suboptimal doses of antigen under the full activation of T cells with different specificity.

Abstract

Loss of tolerance for autoantigens is a common feature in autoimmune diseases. Bystander T-cell activation is the activation of T cells to produce functional changes through TCR-independent stimulation. Although bystander activation may be related to tolerance loss to multiple autoantigens, the activation mechanism of T cells directed to an autoantigen with limited amount is not clear. We investigated an activation mode of T cells (designated as "associator T cells") directed to a suboptimal dose of cognate antigen X in the presence of fully activated T cells (designated as "responder T cells") directed to an optimal dose of antigen Y. In in vitro coculture, the activation of associator T cells was dependent on the presentation of antigen X, and soluble factors from activated responder T cells were not sufficient. Therefore, we conclude this activation mode is different from bystander activation and named it "extended antigen priming (EAP)". T cells with EAP showed a different phenotype compared to conventionally primed cells, suggesting the unique nature of EAP. Intriguingly, EAP was dependent on the CD40-CD40L signaling pathway. Thus, the EAP model is a T-cell activation mode for suboptimal dose of antigen and presumably related to the immune response to autoantigens in autoimmune status.

• Authors: Mihoko Shibuya, Keishi Fujio, Hirofumi Shoda, Tomohisa Okamura, Akiko Okamoto, Shuji Sumitomo, Kazuhiko Yamamoto
• Journal: European journal of immunology (Eur J Immunol) Vol. 45 Issue 6 Pg. 1643-53 (Jun 2015) ISSN: 1521-4141 [Electronic] Germany
• PMID: 25789709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antigens
• Epitopes, T-Lymphocyte
• CD40 Ligand

Topics

• Animals
• Antigen Presentation (immunology)
• Antigen-Presenting Cells (immunology, metabolism)
• Antigens (immunology)
• CD40 Ligand (metabolism)
• Epitopes, T-Lymphocyte (immunology)
• Immunophenotyping
• Lymphocyte Activation (immunology)
• Mice
• Phenotype
• T-Cell Antigen Receptor Specificity (immunology)
• T-Lymphocytes (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)