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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3871-3880.
Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-03-014225.


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IMMUNOBIOLOGY

Differences in the frequency and function of HHV8-specific CD8 T cells between asymptomatic HHV8 infection and Kaposi sarcoma

Marion Lambert, Monique Gannagé, Alexandre Karras, Michal Abel, Christophe Legendre, Delphine Kerob, Felix Agbalika, Pierre-Marie Girard, Celeste Lebbe, and Sophie Caillat-Zucman

From the Institut National de la Santé et de la Recherche Médicale (INSERM), U561 AVENIR Team, Université Paris 5; Hôpital Foch, Service de Néphrologie, Suresnes; Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Necker, Service de Transplantation Rénale, Paris; AP-HP, Hôpital St-Louis, Service de Dermatologie, Université Paris 7, INSERM U716; AP-HP, Hôpital St-Louis, Laboratoire de Virologie, Paris; and AP-HP, Hôpital St-Antoine, Service des Maladies Infectieuses, Paris, France.

It is unclear how the immune response controls human herpesvirus 8 (HHV8; also known as Kaposi sarcoma–associated herpesvirus [KSHV]) replication and thereby prevents Kaposi sarcoma (KS). We compared CD8 T-cell responses to HHV8 latent (K12) and lytic (glycoprotein B, ORF6, ORF61, and ORF65) antigens in patients who spontaneously controlled the infection and in patients with posttransplantation, AIDS-related, or classical KS. We found that anti-HHV8 responses were frequent, diverse, and strongly differentiated toward an effector phenotype in patients who controlled the infection. Conversely, HHV8-specific CD8 cells were very rare in patients who progressed to KS, and were not recruited to the tumoral tissue, as visualized by in situ tetramer staining of KS biopsies. Last, HHV8-specific CD8 T cells were observed in a seronegative recipient of an HHV8infected graft who remained persistently aviremic and antibody negative, suggesting that specific cytotoxic T lymphocytes (CTLs) may provide protection from persistent HHV8 infection. These results support the crucial role of cellular immune responses in controlling HHV8 replication, in preventing malignancies in latently infected subjects, and in conferring genuine resistance to persistent infection. They may also have important implications for the design of prophylactic and therapeutic HHV8 vaccines, and for adoptive immunotherapy of KS.


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