MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants.
The ability of enterotoxin-based mucosal adjuvants to induce CD8+ MHC class I-restricted CTL responses to a codelivered bystander Ag was examined. Escherichia coli heat-labile toxin (LT), or derivatives of LT carrying mutations in the A subunit (LTR72, LTK63), were tested in parallel with cholera to...
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| Fformat: | Journal article |
| Iaith: | English |
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1999
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| _version_ | 1826256516424925184 |
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| author | Simmons, C Mastroeni, P Fowler, R Ghaem-maghami, M Lycke, N Pizza, M Rappuoli, R Dougan, G |
| author_facet | Simmons, C Mastroeni, P Fowler, R Ghaem-maghami, M Lycke, N Pizza, M Rappuoli, R Dougan, G |
| author_sort | Simmons, C |
| collection | OXFORD |
| description | The ability of enterotoxin-based mucosal adjuvants to induce CD8+ MHC class I-restricted CTL responses to a codelivered bystander Ag was examined. Escherichia coli heat-labile toxin (LT), or derivatives of LT carrying mutations in the A subunit (LTR72, LTK63), were tested in parallel with cholera toxin (CT) or a fusion protein consisting of the A1 subunit of CT fused to the Ig binding domain of Staphylococcus aureus protein A (called CTA1-DD). Intranasal (i.n.) immunization of C57BL/6 mice with CT, CTA1-DD, LT, LTR72, LTK63, but not rLT-B, elicited MHC class I-restricted CD8+ T cell responses to coadministered OVA or the OVA CTL peptide SIINFEKL (OVA257-264). CT, LT, and LTR72 also induced CTL responses to OVA after s.c. or oral coimmunization whereas LTK63 only activated responses after s.c. coimmunization. rLT-B was unable to adjuvant CTL responses to OVA or OVA257-264 administered by any route. Mice treated with an anti-CD4 mAb to deplete CD4+ T cells mounted significant OVA-specific CTL responses after i.n. coadministration of LT with OVA or OVA257-264. Both 51Cr release assays and IFN-gamma enzyme-linked immunospot assays indicated that IFN-gamma-/- and IL-12 p40-/- gene knockout mice developed CTL responses equivalent to those detected in normal C57BL/6 mice. The results highlight the versatility of toxin-based adjuvants and suggest that LT potentiates CTL responses independently of IL-12 and IFN-gamma and probably by a mechanism unrelated to cross-priming. |
| first_indexed | 2024-03-06T18:03:28Z |
| format | Journal article |
| id | oxford-uuid:009b8652-ff9a-4bfa-8e01-1597addb7692 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:03:28Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:009b8652-ff9a-4bfa-8e01-1597addb76922022-03-26T08:30:27ZMHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:009b8652-ff9a-4bfa-8e01-1597addb7692EnglishSymplectic Elements at Oxford1999Simmons, CMastroeni, PFowler, RGhaem-maghami, MLycke, NPizza, MRappuoli, RDougan, GThe ability of enterotoxin-based mucosal adjuvants to induce CD8+ MHC class I-restricted CTL responses to a codelivered bystander Ag was examined. Escherichia coli heat-labile toxin (LT), or derivatives of LT carrying mutations in the A subunit (LTR72, LTK63), were tested in parallel with cholera toxin (CT) or a fusion protein consisting of the A1 subunit of CT fused to the Ig binding domain of Staphylococcus aureus protein A (called CTA1-DD). Intranasal (i.n.) immunization of C57BL/6 mice with CT, CTA1-DD, LT, LTR72, LTK63, but not rLT-B, elicited MHC class I-restricted CD8+ T cell responses to coadministered OVA or the OVA CTL peptide SIINFEKL (OVA257-264). CT, LT, and LTR72 also induced CTL responses to OVA after s.c. or oral coimmunization whereas LTK63 only activated responses after s.c. coimmunization. rLT-B was unable to adjuvant CTL responses to OVA or OVA257-264 administered by any route. Mice treated with an anti-CD4 mAb to deplete CD4+ T cells mounted significant OVA-specific CTL responses after i.n. coadministration of LT with OVA or OVA257-264. Both 51Cr release assays and IFN-gamma enzyme-linked immunospot assays indicated that IFN-gamma-/- and IL-12 p40-/- gene knockout mice developed CTL responses equivalent to those detected in normal C57BL/6 mice. The results highlight the versatility of toxin-based adjuvants and suggest that LT potentiates CTL responses independently of IL-12 and IFN-gamma and probably by a mechanism unrelated to cross-priming. |
| spellingShingle | Simmons, C Mastroeni, P Fowler, R Ghaem-maghami, M Lycke, N Pizza, M Rappuoli, R Dougan, G MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. |
| title | MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. |
| title_full | MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. |
| title_fullStr | MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. |
| title_full_unstemmed | MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. |
| title_short | MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. |
| title_sort | mhc class i restricted cytotoxic lymphocyte responses induced by enterotoxin based mucosal adjuvants |
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