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J Immunol. 2007 Aug 15;179(4):2609-15.

Unchecked CD70 expression on T cells lowers threshold for T cell activation in rheumatoid arthritis.

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  • 1Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322, USA.

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.

PMID:
17675524
[PubMed - indexed for MEDLINE]
PMCID:
PMC2832914
Free PMC Article

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