Profiling T cell gene expression in anergy and arthritis

T cells that lose their characteristic ability to proliferate and secrete cytokines in response to antigen stimulation are said to be anergic. Anergy occurs under several different circumstances, suggesting that T cells are poised to become anergic--presumably a protective response that helps limit immune reactions and prevent responses to self antigens. Still, as Ali and colleagues point out, T cells in at least one autoimmune condition, rheumatoid arthritis (RA), are resistant to apoptosis and antigen-stimulation, features that they share with anergic T cell clones.

To explore the idea that anergic cells participate in RA pathogenesis, these authors used differential display to identify genes that are induced or suppressed during the onset of anergy, and they tested RA-associated synovial T cells to determine how well they fit this expression profile. Ali et al. identified 6 transcripts whose up- or down-regulation in RA (as compared to reactive arthritis, a distinct disease, in which T cells remain sensitive to antigens) parallel the changes in expression seen in anergic cells. Several of these are changes are modest or equivocal, but the suppression of calmodulin expression in RA is consistent and dramatic. Ali et al further show that calmodulin expression is restored in patients receiving treatment for RA, and they suggest that regulation of cellular calcium levels represents an important link between the anergic cell and the disease-associated T cell in RA.