Contracted T cell repertoires are found in patients with rheumatoid arthritis (RA), an autoimmune disease linked to HLA class II. In The Journal of Experimental Medicine, Yang et al. identify defects in glucose metabolism in naive and memory CD4+ T cells from patients with RA. RA-associated T cells have lower expression of PFKFB3, a bifunctional enzyme required for commitment to glycolytic metabolism. As a result, those T cells divert glucose to the pentose phosphate pathway, produce less ATP and are more prone to undergo apoptosis than are T cells from healthy people. A lower abundance of PFKFB3 also leads to a decrease in autophagy, which deprives cells of macromolecule reuse. Notably, T cells from patients with systemic lupus erythematosus do not have the same defect, as their T cells have higher expression of PFKFB3. Thus, T cells from patients with RA have intrinsic metabolic defects, but why these cells have lower expression of PFKFB3 remains unknown.

J. Exp. Med. 210, 2119–2134 (2013)