Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro

Abstract

We have studied the pattern of expression of the lymphokines tumor necrosis factor (TNFa) and lymphotoxin (TNFß) in T-cell lines established by transformation with human T-lymphotropic virus, type I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL). We report here that nine of nine HTLV-I, including those with CD4+ or CD8+ as well as CD4-/CD8- phenotypes, constitutively produce high levels of TNFa and -ß mRNA and secrete biologically active TNFß into the culture medium. Similar patterns of expression are seen in six of six HTLV-I-infected T-cell lines directly established from ATL patients. In contrast, several T-cell lines, either uninfected or infected with human immunodeficiency virus I, did not produce comparable levels of the TNFß. Comparisons of a normal functional T-cell clone before and after infection with HTLV-I show that expression of TNFß mRNA is induced in the infected cells. The high level expression in HTLV-I-infected cell lines does not seem to involve perturbation of the TNFa/ß genetic loci by proviral integration. A cell line (81-66/45) nonproductively transformed with HTLV-I that produces tat-1 in the absence of viral structural proteins, produces both TNFa and -ß mRNA. This suggests that expression of these cytokines could be mediated in trans by the tat-1 gene product.