Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection.
Interleukin-2 (IL-2) in combination with the IL-2 receptor has an essential role in antigen-stimulated proliferation of T lymphocytes. It has been proposed that the constitutive expression of the IL-2 receptor on adult T-cell leukaemia (ATL) cells may be associated with transformation of T cells. Although we and others have isolated complementary DNA clones encoding a protein that binds IL-2, formal proof that this protein is the IL-2 receptor requires demonstration of IL-2-dependent growth stimulation of cells expressing the protein. In addition, a functional assay system other than binding of IL-2 is required to investigate the molecular mechanism of signal transmission through the IL-2 receptor using artificially mutated cDNA. The IL-2 receptor expressed in non-lymphoid cells by cDNA transfection did not mediate a growth signal, implying that lymphoid cells expressing the functional receptor might have specific accessory molecule(s) for signal transmission by the receptor. Therefore, we established a line of IL-2-dependent mouse cells (CT/hR) expressing both murine (endogenous) and human IL-2 receptors. Here, by blocking the endogenous mouse IL-2 receptors with monoclonal antibodies, we show that the human IL-2 receptor of CT/hR cells is functionally active. Although CT/hR expressed the human IL-2 receptor constitutively, growth of these cells was strictly dependent on IL-2, indicating that uncontrolled over-expression of the IL-2 receptor was not by itself sufficient for T-cell transformation.
Kondo
S
S
Shimizu
A
A
Maeda
M
M
Tagaya
Y
Y
Yodoi
J
J
Honjo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D004247:DNA / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D015375:Receptors, Interleukin-2; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D004247:DNA