Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 49
Control of Human Herpesvirus Type 8-associated diseases by NK cells
1Maria C. Sirianni, 1Massimo Campagna, 1Donato Scaramuzzi, 1Maurizio Carbonari,
2Elena Toschi, 2Ilaria Bacigalupo, 2Paolo Monini and 2Barbara Ensoli
1Clinical Immunology, Department of Clinical Medicine, University of Rome “La
Sapienza”, 00161 Rome and 2National AIDS Center, Istituto Superiore di Sanita’,
00161 Rome, Italy. E-mail: mariacaterina.sirianni@uniroma1.it
The ‘natural killer’ (NK) cells, a first line defense mechanism against tumors and viruses,
preferentially kill target cells lacking surface Major Histocompatibility Complex class I
(MHC-I) molecule expression. NK cells recognize these targets through membrane receptors,
which can trigger either activating or inhibitory signals for killing. Several tumor or virus
infected cells down-regulate MHC-I expression as a mechanism to evade recognition and
killing by cytotoxic T lymphocytes (CTL). They, however, become targets for NK cells
cytotoxic activity.
NK cell activity is reduced during disease progression in Human Immunodeficiency Virus
(HIV) infection, and in associated tumors latently infected by the oncogenic Human
Herpesvirus Type 8 (HHV8) such as Kaposi’s sarcoma (KS) and primary effusion lymphomas
(PEL). We have demonstrated that HIV-related KS (AIDS-KS) is characterized by an
increased expression on T lymphocytes of inhibitory receptors recognizing HLA-C molecules
(1), whereas non-HIV infected patients with KS (classic KS, C-KS) have a substantial number
of peripheral blood NK cells bearing these receptors (2). NK cells from patients with C-KS,
are equipped with cytolytic molecules including granzyme A and perforin. However, the
cytotoxic activity of NK cells is reduced in patients with C-KS, AIDS-KS or PEL patients,
which are all infected by the HHV8, and this correlates with disease severity (3-5). Moreover,
we have found that HHV8 infected cell lines established from PELs have a reduced surface
expression of MHC-I molecules and are sensitive to the lysis mediated by NK cells (4, 5).
Since PEL cells express the same HHV8 latency program as KS cells, these data point to
MHC-I downregulation by HHV8 as a primary immune evasion mechanism against CTL
responses, further reinforced by up-regulation of inhibitory receptors on T and NK cells in the
setting of HIV and HHV8 infection. Thus, studies on killing receptor regulation and signaling
in T and NK cells may shed light on HHV8-associated tumors both in HIV-infected or non
infected patients.
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