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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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Submitted March 31, 2006
Accepted July 6, 2006
Differences in the frequency and function of HHV8-specific CD8 T cells between asymptomatic HHV8 infection and Kaposi sarcoma
Marion Lambert, Monique Gannage, Alexandre Karras, Michal Abel, Christophe Legendre, Delphine Kerob, Felix Agbalika, Pierre-Marie Girard, Celeste Lebbe, and Sophie Caillat-Zucman*
INSERM, U561 AVENIR TeamU561; Universite Paris 5, Paris, France
Hopital Foch, Service de Nephrologie, Suresnes; Hopital Necker, Paris, France
AP-HP, Hopital Necker, Service de Transplantation renale, Paris, France
AP-HP, Hopital St-Louis, Service de Dermatologie ; Universite PARIS7; INSERM U716
AP-HP, Hopital St-Louis, Laboratoire de Virologie, Paris
AP-HP, Hopital St-Antoine, Service des Maladies Infectieuses, Paris
* Corresponding author; email: caillat{at}paris5.inserm.fr.
It is unclear how the immune response controls human herpes virus 8 (HHV8; also known as Kaposi's 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, ORF65) antigens in patients who spontaneously controlled the infection and in patients with post-transplant, AIDS-related or classical KS. We found that anti-HHV8 responses were frequent, diverse and strongly differentiated towards 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. Lastly, HHV8-specific CD8 T cells were observed in a seronegative recipient of HHV8-infected graft who remained persistently aviremic and antibody-negative, suggesting that specific CTL 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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