title: Scant activation of CD8 T cells by antigen loaded on heat shock protein.
abstract: Heat shock proteins (HSP) not only function as chaperones for denatured proteins but also for antigenic peptides, thus inducing protective T cell responses. Here we show that vaccination with peptide-loaded HSP70 causes initial interferon-gamma production by murine CD8 T cells but no T cell expansion. These CD8 T cells lacked cytotoxic activity in vitro and in vivo, which was not due to apoptosis. Restimulation with peptide-pulsed dendritic cells both bypassed the proliferative block and suspended the non-protective state of CD8 T lymphocytes in an infection model with the bacterial pathogen, Listeria monocytogenes. Cotransfer of antigen-specific CD4 T cells circumvented the proliferative arrest of CD8 T cells. Our data suggest that HSP vaccines induce CD8 T cell unresponsiveness unless proficient help is provided. Assuming that this model reflects the antigenically experienced human condition where immunological space is restricted and any T cell response possibly leads to suppression of heterologous reactions, our findings bear implications for rational vaccination protocols including those for immunocompromised patients.
authors.affiliation: Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Winau
authors.forename: Anne-Marit
authors.initials: AM
authors.lastname: Sponaas
authors.forename: Stephan
authors.initials: S
authors.lastname: Weber
authors.forename: Vera
authors.initials: V
authors.lastname: Schwierzeck
authors.forename: Ralf
authors.initials: R
authors.lastname: Winter
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
chemical_list: D000941:Antigens; D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments