GM-CSF expression is preferential to multi-CSF (IL-3) expression in murine T lymphocyte clones

The expression of the lymphokines GM-CSF and Multi-CSF (IL-3) has been studied in three IL-2-dependent CD4+ T lymphocyte clones. By contrast with the widely held view that lymphokine genes are coordinately expressed, the present study revealed a marked preference for GM-CSF compared with Multi-CSF expression. Preferential expression of GM-CSF was evident in a number of situations: early after stimulation via the T cell antigen receptor; in a proportion of low-producing cells of a clone; and in response to IL-2. There was a clear hierarchy of the three clones studied, each being ranked in the same order in all situations, suggesting that a common mechanism underlies each phenomenon. The possibility that the GM-CSF gene is responsive to lower doses of intercellular signal than the Multi-CSF gene was rendered unlikely, since in only one clone was GM-CSF preferentially expressed at low doses of stimulus. Since GM-CSF expression occurred more rapidly after stimulation, the possibility that Multi-CSF expression is dependent upon that of GM-CSF was considered. However, GM-CSF production was neither necessary nor sufficient for Multi-CSF expression: A retroviral construct expressing a GM-CSF cDNA was introduced into one of the clones, leading to constitutive GM-CSF expression, but Multi-CSF expression was not induced. The possibility is discussed that Multi-CSF expression is dependent on transcriptional activation of the GM-CSF locus and that positive feedback occurs between these two tightly linked genes at the chromosomal level.