γ-Interferon production in peripheral blood mononuclear cells and tumor infiltrating lymphocytes from Kaposi's sarcoma patients: Correlation with the presence of human herpesvirus-8 in peripheral blood mononuclear cells and lesional macrophages

Maria Caterina Sirianni, Laura Vincenzi, Valeria Fiorelli, Simone Topino, Enrico Scala, Stefania Uccini, Antonio Angeloni, Alberto Faggioni, Decio Cerimele, Francesca Cottoni, Fernando Aiuti, Barbara Ensoli

Research output: Contribution to journalArticlepeer-review

Abstract

Evidence indicates that, at least in the early stage, Kaposi's sarcoma (KS) is a cytokine-mediated disease and that it is consistently associated with a novel herpesvirus termed human herpesvirus-8 (HHV-8). To gain insights into the mechanisms by which cytokines and HHV-8 may cooperate in disease pathogenesis, we examined the phenotype, the Th1 (γ-interferon [γIFN]) and Th2 (interleukin-4 [IL-4]) cytokine profile and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC), tumor-infiltrating lymphocytes (TIL), and spindle cell cultures derived from skin lesions of patients affected by classical KS (C-KS) and acquired immunodeficiency syndrome (AIDS)-associated KS (AIDS-KS). TL and spindle cell cultures were examined at day 0 or after culture in conditioned media from activated T cells (TCM) that contain the same cytokines increased in KS tissues. No differences were found in the immunophenotype of PBMC from C-KS patients versus controls, except for AIDS-KS patients who showed a T-CD8+ expansion. However, a preferential infiltration of T-CD8+ cells was found in all KS lesions examined, which was maintained after culture of TIL in TCM. γIFN production was found in both PBMC and cultures derived from all KS examined; some IL-4 positive supernatants were found only in three AIDS-KS cases. Uninvolved skin did not show appreciable lymphocyte infiltration or cytokine production. The culture conditions of the lesional skin allowed also the appearance of adherent, spindle-like cells bearing markers of tissue macrophages. Finally, most or all of the PBMC, lesions, and macrophagic cell cultures from the skin lesions were found to be positive for HHV-8 infection by nested polymerase chain reaction (PCR). These findings indicate that patients with KS express a Th1 phenotype with a prevalent γIFN production, likely accounted for by the local T-CD8+ infiltration. By analogy with other viral infections (ie, Epstein-Barr virus), this suggests that in loco recruitment of lymphoid cells and the subsequent γIFN production may be in response to or elicited by HHV- 8 that was found in both PBMC and macrophagic cell cultures from the lesions of the same patients.

Original languageEnglish
Pages (from-to)968-976
Number of pages9
JournalBlood
Volume91
Issue number3
Publication statusPublished - Feb 1 1998

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'γ-Interferon production in peripheral blood mononuclear cells and tumor infiltrating lymphocytes from Kaposi's sarcoma patients: Correlation with the presence of human herpesvirus-8 in peripheral blood mononuclear cells and lesional macrophages'. Together they form a unique fingerprint.

Cite this