Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody.
A method has been developed to measure the production by single activated T lymphocytes of two hemopoietic growth factors, granulocyte-macrophage CSF (GM-CSF) and multipotential CSF (multi-CSF or IL-3). When individual cells of the L3T4 (CD4)+ F23.1+ T cell clone E9.D4 were transferred by micromanipulation into wells coated with the monoclonal anti-T cell receptor antibody F23.1, up to 90% of cells produced CSF as detected by CSF-dependent hemopoietic cell lines. Production occurred in the absence of proliferation and did not require the addition of accessory cells or IL-2. Both the frequency of CSF-producing cells and the average production per positive cell depended on the density of the immobilized stimulating ligand, indicating that the response of each cell is not an all-or-none phenomenon but varies with the strength of stimulation. Individual cells of the clone varied over a 100-fold range in their total CSF titer with a mean value of about 0.05 U/cell. They also varied in their relative production of GM-CSF and multi-CSF. Thus, low producing cells secreted only GM-CSF whereas high producing cells also secreted multi-CSF. The failure of low producing cells to secrete multi-CSF was not genetically based since such cells could give rise to progeny that synthesized multi-CSF. These results suggest that the synthesis of these two lymphokines can be differentially regulated at the level of the single cell.
Kelso
A
A
Cancer Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Owens
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism*; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D011948:Receptors, Antigen, T-Cell