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. |