Extensive cross-reactivity of CD4+ adenovirus-specific T cells: implications for immunotherapy and gene therapy.
Adenovirus (Ad)-specific T-cell responses in healthy adult donors were investigated. Ad5, inactivated by methylene blue plus visible light, induced proliferation and gamma interferon (IFN-gamma) production in peripheral blood mononuclear cells of the majority of donors. Responding T cells were CD4(+) and produced IFN-gamma upon restimulation with infectious Ad5 and Ads of different subgroups. T-cell clones showed distinct cross-reactivity patterns recognizing Ad serotypes from either one subgroup (C), two subgroups (B and C), or three subgroups (A, B, and C). This cross-reactivity of Ad-specific T cells has relevance both for Ad-based gene therapy protocols, as well as for the feasibility of T-cell-mediated adoptive immunotherapy in recipients of an allogeneic stem cell transplantation.
Department of Pediatrics, Leiden University Medical Center, The Netherlands. B.Heemskerk@lumc.nl
Bianca
B
Heemskerk
Louise A
LA
Veltrop-Duits
Tamara
T
van Vreeswijk
Monique M
MM
ten Dam
Sebastiaan
S
Heidt
Rene E M
RE
Toes
Maarten J D
MJ
van Tol
Marco W
MW
Schilham
D000260:Adenoviruses, Human / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D015316:Genetic Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008751:Methylene Blue / Q000494:pharmacology; D012703:Serotyping; D033581:Stem Cell Transplantation
D007371:Interferon-gamma; D008751:Methylene Blue