Scant activation of CD8 T cells by antigen loaded on heat shock protein.
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.
Winau
Florian
F
Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany.
Sponaas
Anne-Marit
AM
Weber
Stephan
S
Schwierzeck
Vera
V
Winter
Ralf
R
Hurwitz
Robert
R
Kaufmann
Stefan H E
SH
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*
D000941:Antigens; D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments