Clonal heterogeneity in colony stimulating factor production by murine T lymphocytes

Abstract

A panel of 55 alloreactive murine T-lymphocyte clones was screened for the production of granulocyte-macrophage colony stimulating factor (GM-CSF), multilineage CSF (multi-CSF), human-active eosinophil CSF (human-active EO-CSF), and interleukin 2 (IL-2) in response to stimulation with the lectin concanavalin A. Many clones were also characterized for cytolytic specificity and expression of the T-cell antigen receptor-associated surface markers Lyt-2 and L3T4, which reflect their specificity for Class I (H-2K, H-2D) or Class II (H-2l, Mls) histocompatibility antigens, respectively. Eighty percent of the clones secreted detectable quantities of at least one of the four factors measured. Of the factor-producing clones, all appeared to secrete GM-CSF and half also secreted multi-CSF. A subpopulation of multi-CSF producers also released human-active EO-CSF. More than half of the factor-producing clones secreted detectable IL-2; whereas the IL-2-producing clones included some that did not secrete multi-CSF, IL-2 production was always associated with concomitant synthesis of GM-CSF. Comparison of the range and quantities of factors secreted by Lyt-2+ and L3T4+ clones indicated that more L3T4+ clones produced measurable titers of the four factors; on average, this group also secreted 10- to 100-fold higher titers of both the hemopoietic regulators and IL-2 than Lyt-2+ clones. Cells of the L3T4+ phenotype would therefore be expected to account for the majority of CSF and IL-2 secretion by polyclonal populations of activated T lymphocytes.

A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes.

“…There is, however, some evidence for the coordinate induction of subsets of these genes. For example, GM-CSF, G-CSF, and IL-6 mRNAs are induced following TNF-ot treatment of fibroblasts and endothelial cells (40,53) and some mouse T-cell clones coordinately express GM-CSF and IL-3 (20). We have shown that the CK-1 sequence from the G-CSF gene is a TNF-a-responsive element in fibroblasts.…”

Effect of myogenic and adipogenic differentiation on expression of colony-stimulating factor genes.

“…Under resting conditions, monocytic or T-cell production of CSFs is nonexistent or occurs at a low level (3). In response to activation, T cells produce granulocyte-macrophage CSF (GM-CSF) (23) and interleukin (IL)-3 (19), whereas monocytes produce granulocyte (G)-CSF, macrophage CSF (M-CSF; CSF-1), or GM-CSF (8, 14-16, 24, 28, 30). In parallel, IL-1 or tumor necrosis factor alpha treatment of primary cultures of fibroblasts (2,10,18,20,22,25), dermal fibroblasts, fibroblastic cell lines (29,34), and endothelial cells (30,35) results in de novo or increased CSF-1, G-CSF, and/or GM-CSF gene transcription.…”

Nuclear proteins interacting with the promoter region of the human granulocyte/macrophage colony-stimulating factor gene.

“…However, the extended conserved sequence of CK-1 and CK-2 noted above between GM-CSF and IL-3 genes may be involved in T-cell expression of these genes. It is noteworthy that IL-3 and GM-CSF are often coordinately expressed following Con A stimulation of murine T-cell clones (36).…”