Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection

Abstract

Interleukin-2 (IL-2) in combination with the IL-2 receptor has an essential role in antigen-stimulated proliferation of T lymphocytes^1–3. It has been proposed that the constitutive expression of the IL-2 receptor on adult T-cell leukaemia (ATL) cells⁴ may be associated with transformation of T cells^5,6. Although we and others^7–9 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^10,11, 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.