Constitutive Expression of Human Immunodeficiency Virus Type 1 tat Gene Inhibits Interleukin 2 and Interleukin 2 Receptor Expression in a Human CD4 + T Lymphoid (H9) Cell Line

Human immunodeficiency virus (HIV-1) tat, a trans-activator of the HIV long terminal repeat, is essential for HIV replication and causes inhibition of antigen-mediated T cell proliferation. To understand the mechanism of inhibition of T cell proliferation, we have investigated the regulation of IL-2 production and its receptor expression on a human CD4⁺ T lymphoid cell line (H9) transfected with HIV-1 tat gene. When cells were activated by mitogens, as compared to control cells, a significant decrease in both IL-2 mRNA and protein was observed in tat-transfected cells. Similarly, mitogen-induced IL-2Rα and IL-2Rβ mRNA and surface expression of IL-2Rα and IL-2Rβ chains were also significantly decreased in tat-transfected cells compared to control cells. Only IL-2 receptor density was decreased; the affinity of the ligand for the receptor appeared to be unchanged. In contrast to our previous studies with B-lymphoblastoid cell line (Puri RK and Aggarwal BB: Cancer Res 1992;52:3787–3790), IL-4R expression was unaltered by HIV tat transfection in the H9 T cell line, indicating a cell type-specific phenomenon. Owing to the central role of IL-2 in immunoregulation, our data suggest that immunosuppressive effects of HIV-1 tat may be mediated at least in part through the inhibition of both IL-2 production and IL-2 receptor expression.