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- Publisher Website: 10.1046/j.1365-2567.1996.473536.x
- Scopus: eid_2-s2.0-0030023828
- PMID: 8698383
- WOS: WOS:A1996TW13000008
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Article: CD8-deficient mice exhibit augmented mucosal immune responses and intact adjuvant effects to cholera toxin
Title | CD8-deficient mice exhibit augmented mucosal immune responses and intact adjuvant effects to cholera toxin |
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Authors | |
Issue Date | 1996 |
Citation | Immunology, 1996, v. 87, n. 2, p. 220-229 How to Cite? |
Abstract | We used normal, CD4 and CD8 gene-targeted mice to investigate the role of CD4+ and CD8+ T cells in the regulation of gut mucosal immune responses following oral immunizations with cholera toxin (CT) adjuvant. Phenotypic analysis of mucosa-associated tissues revealed normal CD3+ T-cell frequencies in CD4(-/-) and CD8(-/-) mice such that in CD4(-/-) mice the CD8+ and double-negative (DN) T cells were increased. In CD8(-/-) mice the CD4+ T cells were increased, with the exception that in the intraepithelial compartment the CD3+ T cells were predominantly DN γδ T-cell receptor (TCR)+ T cells. All mice, normal and deficient, failed to respond to oral immunization with the antigen, keyhole limpet haemocyanin (KLH), alone. In the presence of CT adjuvant, however, CD8(-/-) mice consistently exhibited three- to fivefold stronger gut mucosal responses compared to normal C57B1/6 mice. By contrast, no difference was observed for systemic responses between CD8(-/-) and normal mice. Thus the up-regulation selectively affected mucosal responses, suggesting that, contrary to the CD8(-/-) mouse gut, the normal gut mucosa may host CD8+ T cells that exert a local suppressive effect on T- and B-cell responses. The magnitude of the enhancing effect of CT was comparable in CD8(-/-) and normal mice, clearly demonstrating that the adjuvant mechanism of CT does not require CD8+ T cells. On the other hand, the adjuvant effect of CT required CD4+ T cells, because no or poor anti-KLH responses were observed in CD4(-/-) mice. In both normal and CD8(-/-) mice CT adjuvant promoted KLH-specific CD4+ T-cell priming without any selective effect on the differentiation towards a T-helper type-1 (Th1) or Th2 dominance. Furthermore, CT adjuvant increased the frequency of CD4+ T cells expressing a memory phenotype, i.e. CD44(high), LECAM-1(low) and CD45RB(low). We have shown, using gene-targeted mice, that CD8+ T cells are not required for the adjuvant effect of CT, and that CD8+ T cells may exert local mucosal down-regulation of intestinal immune responses. |
Persistent Identifier | http://hdl.handle.net/10722/292505 |
ISSN | 2023 Impact Factor: 4.9 2023 SCImago Journal Rankings: 1.720 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Hörnquist, E. | - |
dc.contributor.author | Grdic̀, D. | - |
dc.contributor.author | Mak, T. | - |
dc.contributor.author | Lycke, N. | - |
dc.date.accessioned | 2020-11-17T14:56:37Z | - |
dc.date.available | 2020-11-17T14:56:37Z | - |
dc.date.issued | 1996 | - |
dc.identifier.citation | Immunology, 1996, v. 87, n. 2, p. 220-229 | - |
dc.identifier.issn | 0019-2805 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292505 | - |
dc.description.abstract | We used normal, CD4 and CD8 gene-targeted mice to investigate the role of CD4+ and CD8+ T cells in the regulation of gut mucosal immune responses following oral immunizations with cholera toxin (CT) adjuvant. Phenotypic analysis of mucosa-associated tissues revealed normal CD3+ T-cell frequencies in CD4(-/-) and CD8(-/-) mice such that in CD4(-/-) mice the CD8+ and double-negative (DN) T cells were increased. In CD8(-/-) mice the CD4+ T cells were increased, with the exception that in the intraepithelial compartment the CD3+ T cells were predominantly DN γδ T-cell receptor (TCR)+ T cells. All mice, normal and deficient, failed to respond to oral immunization with the antigen, keyhole limpet haemocyanin (KLH), alone. In the presence of CT adjuvant, however, CD8(-/-) mice consistently exhibited three- to fivefold stronger gut mucosal responses compared to normal C57B1/6 mice. By contrast, no difference was observed for systemic responses between CD8(-/-) and normal mice. Thus the up-regulation selectively affected mucosal responses, suggesting that, contrary to the CD8(-/-) mouse gut, the normal gut mucosa may host CD8+ T cells that exert a local suppressive effect on T- and B-cell responses. The magnitude of the enhancing effect of CT was comparable in CD8(-/-) and normal mice, clearly demonstrating that the adjuvant mechanism of CT does not require CD8+ T cells. On the other hand, the adjuvant effect of CT required CD4+ T cells, because no or poor anti-KLH responses were observed in CD4(-/-) mice. In both normal and CD8(-/-) mice CT adjuvant promoted KLH-specific CD4+ T-cell priming without any selective effect on the differentiation towards a T-helper type-1 (Th1) or Th2 dominance. Furthermore, CT adjuvant increased the frequency of CD4+ T cells expressing a memory phenotype, i.e. CD44(high), LECAM-1(low) and CD45RB(low). We have shown, using gene-targeted mice, that CD8+ T cells are not required for the adjuvant effect of CT, and that CD8+ T cells may exert local mucosal down-regulation of intestinal immune responses. | - |
dc.language | eng | - |
dc.relation.ispartof | Immunology | - |
dc.title | CD8-deficient mice exhibit augmented mucosal immune responses and intact adjuvant effects to cholera toxin | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1046/j.1365-2567.1996.473536.x | - |
dc.identifier.pmid | 8698383 | - |
dc.identifier.pmcid | PMC1384277 | - |
dc.identifier.scopus | eid_2-s2.0-0030023828 | - |
dc.identifier.volume | 87 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 220 | - |
dc.identifier.epage | 229 | - |
dc.identifier.isi | WOS:A1996TW13000008 | - |
dc.identifier.issnl | 0019-2805 | - |