Biochemical and biological properties of interleukin-3: a lymphokine mediating the differentiation of a lineage of cells that includes prothymocytes and mastlike cells.

Abstract

The initial characterization of Interleukin-3 (IL-3) came from a series of studies designed to identify the factors regulating early T-cell differentiation. The approach used took advantage of a series of observations demonstrating that the enzyme 20 α-hydroxysteroid dehydrogenase (20 αSDH) was uniquely associated with the T-cell lineage (Weinstein, 1977; Weinstein et al., 1977; Pepersack et al., 1980). The enzyme is readily detectable in lymphoid tissues of normal mice, in which it is predominantly associated with Thy-1+ cells. The enzyme is either not detectable or occurs at low levels in fetal liver or spleen cells and is absent in spleen cells from genetically athymic or neonatally thymectomized mice. These results demonstrated that 20 αSDH expression is not associated with either B-cell differentiation or the majority of differentiation of myeloid, erythroid, or monocytelike lineages. The in vivo distribution of 20 αSDH was thus most consistent with a unique T-cell lineage expression, which was further supported by examining a variety of tissue-culture cell lines. In particular, 20 αSDH was not detectable in B-cell lines, macrophage/monocyte lines, or erythroid cell lines. In contrast, T-cell lines with a helper phenotype had low levels of 20 αSDH. Cytotoxic IL-2-dependent, T-cell lines were found to have high levels of 20 αSDH. Of particular interest was the observation that terminal transferase (TdT)-positive T-cell lymphomas had no detectable 20 αSDH, consistent with the in vivo data demonstrating that 20 αSDH occurs uniquely in the medullary, hydrocortisone- resistant thymic population. In addition to these data, it has been suggested that 20 αSDH expression is associated with granulopoiesis (Garland and Dexter, 1982, 1983) based on the presence of 20 αSDH in a series of factor-dependent cell lines established from long-term bone marrow cultures.