T lymphocyte control of human eosinophilic granulopoiesis. Clonal analysis in an idiopathic hypereosinophilic syndrome.
The idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders with unknown pathogenesis characterized by persistent peripheral blood and bone marrow eosinophilia and eosinophilic infiltrates of multiple organs leading to severe organ dysfunction. In the present study, T lymphocyte clones were randomly established from the blood of a patient with HES and propagated in culture with mitogen and interleukin 2. Whereas 28 of 29 clones were able to stimulate myeloid colony formation when co-cultured with normal bone marrow cells in a double-layer micro-agar culture system, one third of these clones preferentially stimulated pure eosinophil colonies (up to 98% of all colonies). This pattern differed markedly (p less than 0.001) from the pattern of release of hemopoietic factors by 126 T cell clones established from four other individuals. Eosinophil colony stimulation was due to the release of a lineage-specific eosinophilic colony-stimulating factor (Eo-CSF) by these clones after appropriate stimulation. Production of Eo-CSF in vitro was inhibited by hydrocortisone or cyclosporin A. All Eo-CSF-producing clones had the T4+8-phenotype and were capable of producing in addition interleukin 2 and interferon-gamma. Southern blot analysis of the T cell receptor beta-chain rearrangement of the Eo-CSF-producing clones showed a different rearrangement pattern for each clone. These studies suggest a reactive T cell-mediated eosinophilia as the pathogenetic mechanism in this case of HES and, for the first time, point to a biologic relevance of a lymphokine-induced stimulation of hemopoiesis.
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000473:pathology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002999:Clone Cells / Q000502:physiology; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D003524:Cyclosporins / Q000494:pharmacology; D004802:Eosinophilia / Q000473:pathology*; D004804:Eosinophils / Q000473:pathology*; D006410:Hematopoiesis; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D013577:Syndrome; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D003115:Colony-Stimulating Factors; D003524:Cyclosporins; D006854:Hydrocortisone