NF - ATc 1 levels are increased in murine and human lupus

To the Editor: We read with interest the recent article by Kyttaris and colleagues (1), in which they reported their finding that lupus-prone MRL/lpr mice had increased levels of NF-ATc1 (also known as NF-AT2) in the cytoplasmic and nuclear fractions of freshly isolated lymphocytes, as compared with control lymphocytes from MRL/MpJ mice. They reported no increase in the expression of NF-ATc2 (also known as NFAT1) in the lymphocytes of MRL/lpr mice and contrasted this finding to their observation of increased NF-ATc2 levels in the nucleus of T cells from patients with systemic lupus erythematosus (SLE) (2). We previously reported markedly increased NF-ATc1 levels in CD4 T cells from pediatric patients with SLE as compared with age-, ethnicity-, and sex-matched controls (3). We also observed increased (although less markedly) levels of NF-ATc2 in lupus CD4 T cells compared with controls. This is consistent with the finding by Kyttaris et al in T cells from lupus-prone MRL/lpr mice. NF-ATc2 is expressed constitutively in resting T cell cytoplasm (4,5), whereas NF-ATc1 expression is inducible (6) and up-regulated by NF-ATc2 (7). It has been suggested that NF-ATc1 is the NF-AT family member that is essential for effector T cell development and function (6). Thus, the findings by Kyttaris et al in a mouse model of lupus provide further support for our suggestion that increased NF-ATc1 levels in lupus CD4 T cells represent a more mature/effector T cell phenotype.