Inhibitory effects of human interferons on the immortalization of HUMAN, but not rabbit, T lymphocytes by human T‐lymphotropic virus type‐I (HTLV‐I)

The effects of human interferon (IFN)‐α, ‐β, and ‐γ on the immortalization of human and rabbit lymphocytes by human T‐lymphotropic virus type‐l (HTLV‐I) have been investigated. The immortalization of human peripheral‐blood lymphocytes co‐cultured with lethally X‐ray‐irradiated HTLV‐l‐producer cells, MT‐2, was blocked in the presence of more than 40 u/ml human recombinant IFN‐α or more than 200 u/ml human natural type IFN‐fi. However, rhlFN‐γ did not block immortalization by HTLV‐I even at higher doses. On the other hand, the presence of high doses of hlFN‐α, ‐β, or ‐γ did not exhibit any biological effect on the immortalization of rabbit peripheral‐blood lymphocytes co‐cultured with lethally X‐ray‐irradiated MT‐2 cells. Integration of the full length of HTLV‐I genome was detected in every transformant by Southern blot analysis. All cell lines established were CD4⁺/CD8^÷ T‐lymphocytes, except for one cell line of CD4⁺/CD8⁺. Morphologically intact HTLV‐I production was observed by electron microscopy in these cells. Our results indicate that HTLV‐I released under the strongly suppressed condition in the presence of IFNs remains active and able to immortalize T lymphocytes. It is also suggested that immortalization of human T lymphocytes by HTLV‐I can be inhibited by the antiviral state induced by the treatment with low doses of hlFN‐α and ‐β, whereas immortalization of rabbit T lymphocytes is not inhibited because of the species specificity of hlFNs.