Work

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Year: 2007

Type: article

Abstract: Rheumatoid arthritis (RA) is characterized by premature immune aging with accumulation of degenerate T cells deficient for CD28. Gene expression profiling of CD4(+)CD28(-) and CD4(+)CD28(+) T cells to discover disease-promoting activities of CD28(-) T cells identified expression of CD70 as a most striking difference. Hence, CD70 was significantly more expressed in CD4 T cells from RA patients compared with age-matched controls (p < 0.006). The underlying mechanism was a failure to repress CD70 expression after activation-dependent induction. This defect in RA was not related to differential promoter demethylation. CD70 on bystander CD4(+)CD28(-) T cells functioned by lowering the threshold for T cell activation; admixture of CD4(+)CD28(-) T cells augmented TCR-induced responses of autologous naive CD4(+)CD28(+) T cells, particularly of low-avidity T cells. The data support a model in which CD70 expressed on T cells causes degeneracy in T cell responses and undermines tolerance mechanisms that normally control T cell autoreactivity.

Source: The Journal of Immunology

DOI: 10.4049/jimmunol.179.4.2609

Authors: Won-Woo Lee, Zhi-Zhang Yang, Guangjin Li, Cornelia M Weyand, Jörg J Goronzy

Institutions: Emory University, Mayo Clinic

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases