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-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, and
Barbara Ensoli
From the Departments of Allergy and Clinical Immunology and
Experimental Medicine and Pathology, University of Rome "La
Sapienza," Rome; the Department of Dermatology, Catholic University
of Rome, Rome; the University of Sassari, Sassari; and the Laboratory
of Virology, Istituto Superiore di Sanità, Rome, Italy.
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
( -interferon [ IFN]) 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).
TIL 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. IFN 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 IFN 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
IFN 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.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 968-976
© 1998 by The American Society of Hematology.

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