Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro.
We have studied the pattern of expression of the lymphokines tumor necrosis factor (TNF alpha) and lymphotoxin (TNF beta) 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-infected T-cell lines, established by in vitro infection with HTLV-I, including those with CD4+ or CD8+ as well as CD4-/CD8- phenotypes, constitutively produce high levels of TNF alpha and -beta mRNA and secrete biologically active TNF beta 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 TNF beta. Comparisons of a normal functional T-cell clone before and after infection with HTLV-I show that expression of TNF beta mRNA is induced in the infected cells. The high level expression in HTLV-I-infected cell lines dose not seem to involve perturbation of the TNF alpha/beta 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 TNF alpha and -beta mRNA. This suggests that expression of these cytokines could be mediated in trans by the tat-1 gene product.
Tschachler
E
E
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892.
Robert-Guroff
M
M
Gallo
R C
RC
Reitz
M S
MS
D015139:Blotting, Southern; D002460:Cell Line; D002474:Cell-Free System; D002999:Clone Cells / Q000378:metabolism; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000302:isolation & purification*; D010641:Phenotype; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000302:isolation & purification; D012191:Retroviridae Proteins / Q000032:analysis; D013601:T-Lymphocytes / Q000032:analysis / Q000145:classification; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification / Q000378:metabolism
D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D012191:Retroviridae Proteins; D014409:Tumor Necrosis Factor-alpha