title: Differences in the frequency and function of HHV8-specific CD8 T cells between asymptomatic HHV8 infection and Kaposi sarcoma.
abstract: 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.
authors.affiliation: INSERM U561, Hôpital St-Vincent de Paul, 75014 Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Lambert
authors.forename: Monique
authors.initials: M
authors.lastname: Gannagé
authors.forename: Alexandre
authors.initials: A
authors.lastname: Karras
authors.forename: Michal
authors.initials: M
authors.lastname: Abel
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Delphine
authors.initials: D
authors.lastname: Kerob
authors.forename: Felix
authors.initials: F
authors.lastname: Agbalika
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Celeste
authors.initials: C
authors.lastname: Lebbe
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000368:Aged; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D019288:Herpesvirus 8, Human / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D008875:Middle Aged; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology / Q000473:pathology; D012514:Sarcoma, Kaposi / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D019737:Transplants / Q000009:adverse effects; D014779:Virus Replication / Q000276:immunology*
chemical_list: D000957:Antigens, Viral, Tumor; D019496:Cancer Vaccines; D022283:Herpesvirus Vaccines