[Experimental principles of therapy-oriented pathogenetic classification of aplastic anemia in childhood].
Growth and differentiation of hematopoietic progenitor cells is regulated by a complex network of stimulatory and inhibitory cytokines. Bone marrow failures can be due to a decrease of stimulators or an increase of inhibitors. T cells produce both, hematopoiesis stimulating and inhibiting cytokines. Therefore, a role of T cells in regulating hematopoiesis can only be assumed if the gene expression of these antagonistic acting cytokines can be differentially induced in T cells. To establish a model of selective cytokine induction, we investigated the induction of IFN gamma as inhibitor and GM-CSF as stimulator of hematopoiesis in T cells. Our results showed that IFN gamma mRNA accumulates in T cells which have been pre-activated via the signal transduction unit CD3, but not in unstimulated T cells. This accumulation depends on the expression of the high affinity IL2 receptor which is including the IL2 receptor alpha-chain (IL2R alpha, CD25). In a study on children with constitutional (CAA) versus acquired aplastic (EAA) anemia, we investigated the relevance of this model for the pathogenesis of aplastic anemia in childhood. We compared the following parameters: 1. Incidence of hematopoietic progenitor cells and cloning efficiency, 2. activation status and IL2R alpha expression of bone marrow T cells, 3. T cell cytokine expression profile. Our results show: 1. The relative incidence of bone marrow progenitor cells is decreased in children with CAA and normal in children with EAA. 2. Clonogenic growth of hematopoietic progenitor cells is suppressed in children with EAA.(ABSTRACT TRUNCATED AT 250 WORDS)
Burdach
S
S
Labor für experimentelle Hämatologie und Knochenmarktransplantation, Heinrich Heine-Universität, Düsseldorf.
Vöhringer
R
R
Dilloo
D
D
Krauth
K
K
Hanenberg
H
H
Göbel
U
U
D000741:Anemia, Aplastic / Q000145:classification* / Q000209:etiology / Q000628:therapy; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation; D002648:Child; D016207:Cytokines / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D015375:Receptors, Interleukin-2
Experimentelle Grundlagen einer Therapie-orientierten pathogenetischen Klassifikation der Aplastischen Anämie im Kindesalter.