Down-regulation of natural killer cells and of g/d T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity?

Abstract

A depletion of natural killer (NK) cells seems to play a role in the course of systemic lupus erythematosus (SLE) whereas the possible involvement in this disease of T cell receptor (TCR) g/d positive T cells is still debated. The aim of this study was to evaluate the peripheral blood mononuclear cells (PBMCs) that express NK surface markers CD16 and CD56 or g/d TCR antigen in 58 SLE patients, investigating the possible role of these cell subsets involved in non-MHC-restricted cytotoxicity and their relationship with the main clinical and laboratory parameters. SLE patients had, with respect to controls, considerably decreased values of NK cells (P < 0.0004 in percentage and P < 0.00004 as absolute number), of non-MHC-restricted T cytotoxic lymphocytes (P < 0.007 and P < 0.0015, respectively) and of T cells expressing g/d TCR (P < 0.02 and P < 0.004, respectively). The absolute numbers of these cell subsets positively correlated to each other (P < 0.009). g/d T cells inversely correlated with higher ESR values, both percentually (P < 0.006; r ‘ 70.367) and in absolute number (P < 0.009; r ‘ 70.350). Moreover, the percentage values of this cell subset inversely correlated with higher levels of CRP (P < 0.05; r ‘ 70.256) while SLE patients with anti-SSB/La antibodies had lower values of T lymphocytes bearing g/d TCR, both as percentage (P < 0.008) and as absolute number (P < 0.02). Our study indicates that non-MHC-restricted cytotoxicity, shared by NK, NK-like and g/d T cells, may be down-regulated in SLE patients, owing to a significant reduction of these PBMC subsets. These specific cell subset impairments seem to affect only some aspects of the disease, suggesting a weakening of the regulatory properties of these cells in the control of different immunological and inflammatory features of SLE, that could be of importance in its clinical expression.