Dissociated expression of granulocyte-macrophage CSF and IL-3 in short-term T cell clones from normal mice.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 are generally thought to be produced in a coordinated fashion by all activated T cells. We have examined this premise using quantitative kinetic analyses of the expression of GM-CSF and IL-3 in clonal cultures of mouse T cells for the first two weeks following in vitro stimulation with solid-phase TCR- and accessory molecule-specific mAbs. We demonstrate that 1) differential secretion of GM-CSF and IL-3 is a feature of high proportions of CD8+ and CD4+ T cell clones, for extended periods of time following activation; 2) multiple patterns of expression of these two cytokines can occur, including equivalent, GM-CSF-biased, and IL-3-biased production, and a pattern that switches over a period of days from GM-CSF-biased to IL-3-biased production; 3) the disparate relative levels of secretion are not due to differential consumption of either cytokine; 4) altered T cell activation by addition of CD28 costimulation accelerates both GM-CSF and IL-3 production but biased patterns of expression are retained, and 5) most T cells are not pre-committed to a particular pattern of relative GM-CSF and IL-3 expression; instead, the potential for multiple patterns may persist for several days following in vitro activation. The results indicate that T cells have the potential to display previously unrecognized diversity of expression of GM-CSF and IL-3.
Fitzpatrick
D R
DR
Transplantation Biology Unit, Queensland Institute of Medical Research, Australia.
Kelso
A
A
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002999:Clone Cells; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000378:metabolism; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D018106:CD28 Antigens; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor