The relative roles of interleukins 1, 2, and 3 in the regulation of T cell differentiation.
The initial description and purification of IL 3 was based on its potential relevance in early T cell differentiation. Although the data do not provide conclusive evidence for a role of IL 3 in T cell differentiation, a number of observations provide some indications that a relationship exists. The most intriguing aspects are concerned with the distribution and regulation of expression of 20 alpha SDH. This particular marker is interesting since it may allow studies of aspects of T cell differentiation that have not been possible with more conventional approaches. The available data are consistent with the hypothesis that in the bone marrow there exists a stem cell that in response to IL 3 is induced to differentiate including the induction of expression of 20 alpha SDH and Thy 1+. Phenotypically this induced cell is similar to a medullary thymocyte, although the cells derived in vitro clearly do not have the functional characteristics of medullary thymocytes. It can be rationalized that a bone marrow-induced prothymocyte may require the thymic microenvironment for continued maturation. Irrespective of this, it now becomes necessary to further explore the possibilities by extending the approaches used to define and study early bone marrow-localized pre-T cell populations as well as continuing to define the necessary components of the thymus in the differentiation pathway for T cells. In these areas of research the experience and systems derived from studies of long-term bone marrow cultures will be of considerable value. In addition to the proposed role that IL 3 plays in early T cell differentiation, it is apparent that the stem cell that is induced to differentiate may have considerably more potentials than the T cell lineage. The ability of IL 3 to induce the differentiation of 20 alpha SDH-positive mastlike cells in vitro is the most demonstrable functional phenotype. The absolute requirement of Il 3 throughout the differentiation of such cells indicates that in vivo, where IL 3 is generally not detectable, the frequency with which such progeny are obtained may be quite low and restricted to unique immunological situations in which high levels of IL 3 are produced. In addition, it appears likely that IL 3 induces the differentiation of a cell that in the presence of erythropoietin can be induced to differentiate along an erythroid pathway. Last, IL 3 may induce the differentiation of promyeloblasts that can differentiate in the presence of CSF-2 [unpublished data].(ABSTRACT TRUNCATED AT 400 WORDS)
D015089:20-Hydroxysteroid Dehydrogenases / Q000032:analysis; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D007377:Interleukin-3; D007942:Leukemia, Experimental / Q000473:pathology; D008222:Lymphokines / Q000502:physiology*; D008223:Lymphoma / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology* / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D008222:Lymphokines; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D004253:DNA Nucleotidylexotransferase