2295) show that T cells also have their own internal barrier to self-reactivity—a transcription factor called Egr-2.
The team had previously found that Egr-2 is made by T cells that are repeatedly stimulated by their cognate antigen. The cells then become unresponsive, much like T cells that are constantly exposed to self-antigens in the periphery.
The authors now find that, in mice, Egr-2 expression is also turned on in effector T cells that develop as a result of exposure to gut bacteria or to certain self-antigens. The Egr-2–expressing cells reacted to strong T cell receptor stimulation in vitro but did not trigger autoimmunity or responses against the gut bacteria in mice, suggesting that Egr-2 might only temper T cell reaction to the relatively weak signals of self-antigens. But how repeated antigen stimulation induces Egr-2 and how the transcription factor distinguishes weak, self-signals from strong, non-self signals are not yet known.
The deletion of Egr-2 triggered the accumulation of effector T cells and the development of lupus and its accompanying inflammation. The T cells amassed due to reduced expression of the gene for the cell cycle inhibitor p21Cip1, one of the few known Egr-2 targets. The rapidly proliferating T cells overexpressed genes for inflammatory cytokines, but the authors have yet to determine which Egr-2–induced genes normally suppress these cytokine genes.
Persistent viral antigens are known to induce tolerance in effector T cells, resulting in chronic infections. The group is now investigating whether deletion of Egr-2 in these cells prevents chronic infection. HB