Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis.

Authors

• Guang-Xian Zhang
• Shuo Yu
• Bruno Gran
• Jifen Li
• Ines Siglienti
• Xiaohan Chen
• Divina Calida
• Elvira Ventura
• Malek Kamoun
• Abdolmohamad Rostami

Publication/Presentation Date

11-1-2003

Abstract

IL-12 was thought to be involved in the development of experimental autoimmune encephalomyelitis (EAE), a Th1 cell-mediated autoimmune disorder of the CNS. However, we have recently found that IL-12 responsiveness, via IL-12Rbeta2, is not required in the induction of EAE. To determine the role of IL-12Rbeta1, a key subunit for the responsiveness to both IL-12 and IL-23, in the development of autoimmune diseases, we studied EAE in mice deficient in this subunit of IL-12R. IL-12Rbeta1(-/-) mice are completely resistant to myelin oligodendrocyte glycoprotein (MOG)-induced EAE, with an autoantigen-specific Th2 response. To study the mechanism underlying this Th2 bias, we cocultured purified CD4(+) T cells and APCs of MOG-immunized mice. We demonstrate that IL-12Rbeta1(-/-) APCs drive CD4(+) T cells of both wild-type and IL-12Rbeta1(-/-) mice to an Ag-induced Th2 phenotype, whereas wild-type APCs drive these CD4(+) T cells toward a Th1 type. IL-12Rbeta1(-/-) CD4(+) T cells, in turn, appear to exert an immunoregulatory effect on the capacity of wild-type APCs to produce IFN-gamma and TNF-alpha. Furthermore, decreased levels of IL-12p40, p35, and IL-23p19 mRNA expression were found in IL-12Rbeta1(-/-) APCs, indicating an autocrine pathway of IL-12/IL-23 via IL-12Rbeta1. IL-18 production and IL-18Ralpha expression are also significantly decreased in IL-12Rbeta1(-/-) mice immunized with MOG. We conclude that in the absence of IL-12Rbeta1, APCs play a prominent regulatory role in the induction of autoantigen-specific Th2 cells.

Volume

171

Issue

9

First Page

4485

Last Page

4492

ISSN

0022-1767

Published In/Presented At

Zhang, G. X., Yu, S., Gran, B., Li, J., Siglienti, I., Chen, X., Calida, D., Ventura, E., Kamoun, M., & Rostami, A. (2003). Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950), 171(9), 4485–4492. https://doi.org/10.4049/jimmunol.171.9.4485

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

14568921

Department(s)

Administration and Leadership

Document Type

Article