Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression implications for AIDS-kaposi's sarcoma pathogenesis

Giovanni Barillari, Luigi Buonaguro, Valeria Fiorelli, John Hoffman, Frank Michaels, Robert C. Gallo, Barbara Ensoli

Research output: Contribution to journalArticlepeer-review

Abstract

Kaposi's sarcoma (KS) arises more frequently in homosexual and bisexual men than in other groups of HIV-1 infected individuals. Clinico-epidemiologic data indicate that homosexuals often are infected with multiple microbial agents and/or subjected to other antigenic stimuli, preceding or accompanying HIV-1 infection. Signs of immune activation, in fact, frequently have been detected in these individuals, and the onset of KS can precede any sign of immunodeficiency. These data have suggested that products from activated immune cells may affect the development of AIDS-KS. Here we report that conditioned media from activated or dysregulated T cells contain a variety of cytokines that promote the growth of spindle cells derived from KS lesions of AIDS patients (AIDS-KS cells) and induce normal vascular cells, potential cell progenitors of the AIDS-KS cells, to acquire features of the KS cell phenotype ("spindle" cell morphology and growth responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein). The same conditioned media or cytokines promote HIV-1 gene expression and rescue defective HIV-1 proviruses, interrupting HIV-1 latency and increasing Tat production. The cellular and viral effects of cytokines are increased in an additive or synergistic manner by picomolar concentrations of extracellular Tat. These data suggest that cytokines produced by activated immune cells cooperate with HIV-1 infection in AIDS-KS pathogenesis.

Original languageEnglish
Pages (from-to)3727-3734
Number of pages8
JournalJournal of Immunology
Volume149
Issue number11
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Immunology

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