Spontaneous production of interleukin 3 by T lymphocytes from autoimmune MRL/MP‐lpr/lpr mice

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Abstract
MRL/MP‐lpr/lpr (MRL/lpr) mice develop a lupus‐like autoimmune disease and a massive generalized lymphadenopathy associated with proliferation of nonmalignant Thy‐1+ Lyt‐1+ cells. The mechanism(s) leading to outgrowth of these cells is unknown. We report here that Thy‐1+, Lyt‐1+, Lyt‐2− lymphocytes from spleens of MRL/lpr mice, but not from several strains of normal mice, spontaneously secrete IL3. The presence of IL3 is shown by: (a) the ability of the supernatants from unstimulated spleen cells of MRL/lpr (MRL/lpr SUP) to support growth of IL3 but not IL2 addicted cells and (b) the growth‐promoting activity in MRL/lpr SUP was absorbed with IL3‐dependent cells but not with IL2‐dependent cells. Spontaneous release of IL3 was detected in supernatants from spleen cells of 6‐week‐old MRL/lpr mice and the titers of IL3 activity increased with age. Nylon wool‐enriched cells from spleens of MRL/lpr mice proliferated in response to purified IL3 and IL3 secreted by MRL/lpr T cells, in a manner similar to nylon wool‐passed cells from normal mice. The cells responding to both sources of IL3 were Thy‐1+, Lyt‐1+, Lyt‐2−. Thus, Thy‐1+, Lyt‐1+,2− cells from spleen of MRL/lpr mice spontaneously secrete IL3 and respond normally to this lymphokine. Four Thy‐1+, Lyt‐1+,2− cell lines derived from unstimulated spleen cells of MRL/lpr mice were established in culture with IL3. These IL3‐sensitive T cell lines help syngeneic and H‐2‐compatible normal small “resting” B cells to mature into plasma cells secreting predominantly IgG1, IgG2 and IgA. Taken together, these data and previous findings that T cells from MRL/lpr mice have an impaired production of and response to IL2, strongly suggest that abnormal production of IL3 may account for the outgrowth of Thy‐1+, Lyt‐1+,2− cells in the MRL/lpr mouse. Finally, a mechanism linking abnormal production of IL3 and B cell hyperactivity in these animals is proposed.