Similarly, a CD4+CD25lowFoxP3+ Treg population has been observed in SLE patients, and given that SLE patients have a prematurely aged immune system with accumulation of CD28− T-cells (49), it is conceivable that (at least part of) this CD4+ CD25lowFoxP3+ Treg population was CD28−. This evidence concerns the gene CD28 and systemic lupus erythematosus.