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Publication : Scant activation of CD8 T cells by antigen loaded on heat shock protein.

First Author  Winau F Year  2005
Journal  Eur J Immunol Volume  35
Issue  4 Pages  1046-55
PubMed ID  15739167 Mgi Jnum  J:97820
Mgi Id  MGI:3576445 Doi  10.1002/eji.200425603
Citation  Winau F, et al. (2005) Scant activation of CD8 T cells by antigen loaded on heat shock protein. Eur J Immunol 35(4):1046-55
abstractText  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.
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