Interleukin 2 (IL-2) receptor expression and sensitivity to diphteria fusion toxin DAB389IL-2 in cultured hematopoietic cells.
The high-affinity interleukin 2 (IL-2) receptor is a heterotrimer consisting of alpha, beta, and gamma subunits. We examined the concentration of subunit mRNA for each of the three protein subunits on human hematopoietic cell lines, human peripheral blood mononuclear cells, and murine fibroblasts transfected with cDNAs encoding the human IL-2 receptor subunits. In most cultured hematopoietic cells, there was abundant gamma subunit message. In contrast, there was variable expression of both alpha and beta subunit message. Sensitivity of cells to the diphtheria fusion toxin DAB389IL-2 was not related to expression of any single IL-2 receptor subunit mRNA. Rather, the greatest sensitivity was observed for cells possessing all three subunit mRNAs. Cells displaying beta and gamma subunit mRNA showed a reduced but significant sensitivity to the fusion toxin. In contrast, cells with alpha and gamma subunit mRNA, but missing the beta subunit mRNA, were insensitive to DAB389IL-2. The data correlate with the requirement for an intermediate or a high-affinity receptor for cell intoxication. A critical concentration of the beta subunit may be required for toxin internalization and killing.
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Department of Pathology, Medical University of South Carolina, Charleston 29425, USA.
Waters
C
C
Poisson
L
L
Willingham
M C
MC
Sugamura
K
K
Frankel
A E
AE
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D004167:Diphtheria Toxin / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D000922:Immunotoxins / Q000633:toxicity*; D007376:Interleukin-2 / Q000633:toxicity*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox