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.
Original language | English |
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Pages (from-to) | 2609-2615 |
Number of pages | 7 |
Journal | Journal of Immunology |
Volume | 179 |
Issue number | 4 |
DOIs | |
State | Published - 15 Aug 2007 |