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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1. Verfasser: Simmons, Cameron
Format: Journal Article
Sprache:Englisch
Veröffentlicht: 2018
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.
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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