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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| Format: | Journal Article |
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2018
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| Online-Zugang: | https://demo7.dspace.org/handle/123456789/201 |
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| author | Simmons, Cameron |
| author_browse | Simmons, Cameron |
| author_facet | Simmons, Cameron |
| author_sort | Simmons, Cameron |
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| 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. |
| format | Journal Article |
| id | oai:localhost:123456789-201 |
| institution | DSPACE.FCHPT |
| language | English |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
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| spelling | oai:localhost:123456789-2012021-04-07T16:30:08Z MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants Simmons, Cameron 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. 2018-09-14T11:15:06Z 2017-07-05T02:44:24Z 2018-09-14T11:15:06Z 1999-12-15 Journal Article https://demo7.dspace.org/handle/123456789/201 English |
| spellingShingle | Simmons, Cameron 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 |
| url | https://demo7.dspace.org/handle/123456789/201 |
| work_keys_str_mv | AT simmonscameron mhcclassirestrictedcytotoxiclymphocyteresponsesinducedbyenterotoxinbasedmucosaladjuvants |