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 IFNγ as inhibitor and GM-CSF as stimulator of hematopoiesis in T cells. Our results showed that IFNγ 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 α-chain (IL2Rα, 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 IL2Rα 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. 3. Native T cells of children with CAA show an increased induction capacity of IFNγ production, however, the induction capacity in children with CAA is normal. 4. Children with EAA show an increased incidence of activated, IL2 expressing T cells in the bone marrow. Based on these results we would like to propose the following therapy-based classification of childhood aplastic anemias: Aplastic anemias type I (CAA) is due to a reduction in the progenitor cell pool. Therefore, bone marrow transplantation would be the treatment of choice. In contrast, aplastic anemias type II (EAA) are caused by immunological suppression of the progenitor cell growth. In these patients, immunosuppression or -modulation would be the treatment of choice.
|Translated title of the contribution||Experimental basis of a therapy-oriented pathogenetic classification of aplastic anemia in childhood|
|Number of pages||7|
|State||Published - Jan 1 1994|
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health