Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S).
The derivation of subline of CTLL cells that grow in IL-4/B cell stimulatory factor-1 is described. These cells, designated CT.4R cells, were obtained by extended culture of the CTLL line CT.EV in IL-4. CT.4R cells are highly responsive to both IL-4 and IL-2. Mutagenesis of CT.4R cells with ethylmethane sulfonate and selection for lack of expression of the p55 chain of the IL-2R was carried out and a clone was selected that was hyporesponsive to IL-2 but retained full sensitivity to IL-4. These cells, designated CT.4S cells, develop a very meager response to IL-2 at concentrations of 100 U/ml or less although that display vigorous responses to higher IL-2 concentrations. CT.4S cells give measurable responses to 3-10 U/ml (approximately 15-50 pg/ml) of IL-4. CT.4R and CT.4S cells fail to respond to IL-1, IL-3, IL-6, granulocyte-macrophage-CSF, granulocyte-CSF, CSF-1 or IFN-gamma. Thus, CT.4S cells can be used as a sensitive and specific bioassay for IL-4. ID CT.4R cells can be grown in either IL-4 or IL-2. When grown in IL-4, CT.4R cells express small amounts of the p55 chain of the IL-2R but rapidly upregulate their level of expression of p55 when IL-2 is added and rapidly diminish p55 expression when IL-2 is removed. Thus, although IL-2 and IL-4 both stimulate vigorous growth responses by CT.4R cells, they differ in their capacity to induce the expression of the p55 chain implying that their mechanisms of T cell stimulation are not identical.
Hu-Li
J
J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Ohara
J
J
Watson
C
C
Tsang
W
W
Paul
W E
WE
D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D007378:Interleukins; D015375:Receptors, Interleukin-2; D015847:Interleukin-4