Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help

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  • Sally R.M. Bennett
    From the *Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; ‡Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, QLD 4029, Australia; and §The Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia
  • Francis R. Carbone
    From the *Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; ‡Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, QLD 4029, Australia; and §The Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia
  • Freda Karamalis
    From the *Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; ‡Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, QLD 4029, Australia; and §The Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia
  • Jacques F.A.P. Miller
    From the *Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; ‡Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, QLD 4029, Australia; and §The Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia
  • William R. Heath
    From the *Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; ‡Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, QLD 4029, Australia; and §The Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia

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<jats:p>Class I–restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I–restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow–derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.</jats:p>

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