Natural killer cell-mediated activity in mixed connective tissue disease and its response to induction by interleukin-2

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Abstract
We studied natural killer cell-mediated (NKCM) activity and its enhancement by interleukin-2 (IL-2) in 15 patients with mixed connective tissue disease (MCTD). The mean baseline NKCM activity of peripheral blood mononuclear cells (MNC) against K562 target cells in the51Cr release assay was found to be similar to that found in age/sexmatched controls. MCTD patients' cells, however, responded significatively less to IL-2 induction of NKCM than did those of the controls. Using the single-cell agarose NK assay, we found that MCTD patients have a small number of active NK cells that exhibit a high rate of recycling capacity in the baseline state. These preactivated cells could not be stimulated further by IL-2. In two MCTD patients the response to IL-2 was nil, and in the serum from both of them we found an IgM inhibitory factor of such IL-2-induced enhancement. This factor could be absorbed only partially by normal MNC and NK cell-depleted MNC but completely by an IL-2-dependent T-cell line, suggesting that the inhibitory factor may be acting on the IL-2 receptor. These findings seem to be different from those reported in systemic lupus erythematosus and strengthen the notion that MCTD is due to a different immunoregulatory aberration.