Spontaneous production of interleukin 3 by T lymphocytes from autoimmune MRL/MP-lpr/lpr mice.
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+, Lyt2- 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.
D000483:Alleles; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D004261:DNA Replication; D004195:Disease Models, Animal; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics; D007377:Interleukin-3; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens; D007377:Interleukin-3; D008222:Lymphokines