Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients.
BACKGROUND:Crohn's disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is unknown, but an excessive immune response to bacteria in genetically susceptible individuals is probably involved. The response is characterized by a strong Th1/Th17 response, but the relat...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-05-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2682569?pdf=render |
| _version_ | 1818987139492216832 |
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| author | Ingrid Olsen Stig Tollefsen Claus Aagaard Liv J Reitan John P Bannantine Peter Andersen Ludvig M Sollid Knut E A Lundin |
| author_facet | Ingrid Olsen Stig Tollefsen Claus Aagaard Liv J Reitan John P Bannantine Peter Andersen Ludvig M Sollid Knut E A Lundin |
| author_sort | Ingrid Olsen |
| collection | DOAJ |
| description | BACKGROUND:Crohn's disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is unknown, but an excessive immune response to bacteria in genetically susceptible individuals is probably involved. The response is characterized by a strong Th1/Th17 response, but the relative importance of the various bacteria is not known. METHODOLOGY/PRINCIPAL FINDINGS:In an attempt to address this issue, we made T-cell lines from intestinal biopsies of patients with CD (n = 11), ulcerative colitis (UC) (n = 13) and controls (n = 10). The T-cell lines were tested for responses to various bacteria. A majority of the CD patients with active disease had a dominant response to Mycobacterium avium subspecies paratuberculosis (MAP). The T cells from CD patients also showed higher proliferation in response to MAP compared to UC patients (p<0.025). MAP reactive CD4 T-cell clones (n = 28) were isolated from four CD patients. The T-cell clones produced IL-17 and/or IFN-gamma, while minimal amounts of IL-4 were detected. To further characterize the specificity, the responses to antigen preparations from different mycobacterial species were tested. One T-cell clone responded only to MAP and the very closely related M. avium subspecies avium (MAA) while another responded to MAP, MAA and Mycobacterium intracellulare. A more broadly reactive T-cell clone reacted to MAP1508 which belongs to the esx protein family. CONCLUSIONS/SIGNIFICANCE:The presence of MAP reactive T cells with a Th1 or Th1/Th17 phenotype may suggest a possible role of mycobacteria in the inflammation seen in CD. The isolation of intestinal T cells followed by characterization of their specificity is a valuable tool to study the relative importance of different bacteria in CD. |
| first_indexed | 2024-12-20T19:01:56Z |
| format | Article |
| id | doaj.art-f2bf05443f4a41ee8058bed52932fb1d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T19:01:56Z |
| publishDate | 2009-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f2bf05443f4a41ee8058bed52932fb1d2022-12-21T19:29:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-05-0145e564110.1371/journal.pone.0005641Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients.Ingrid OlsenStig TollefsenClaus AagaardLiv J ReitanJohn P BannantinePeter AndersenLudvig M SollidKnut E A LundinBACKGROUND:Crohn's disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is unknown, but an excessive immune response to bacteria in genetically susceptible individuals is probably involved. The response is characterized by a strong Th1/Th17 response, but the relative importance of the various bacteria is not known. METHODOLOGY/PRINCIPAL FINDINGS:In an attempt to address this issue, we made T-cell lines from intestinal biopsies of patients with CD (n = 11), ulcerative colitis (UC) (n = 13) and controls (n = 10). The T-cell lines were tested for responses to various bacteria. A majority of the CD patients with active disease had a dominant response to Mycobacterium avium subspecies paratuberculosis (MAP). The T cells from CD patients also showed higher proliferation in response to MAP compared to UC patients (p<0.025). MAP reactive CD4 T-cell clones (n = 28) were isolated from four CD patients. The T-cell clones produced IL-17 and/or IFN-gamma, while minimal amounts of IL-4 were detected. To further characterize the specificity, the responses to antigen preparations from different mycobacterial species were tested. One T-cell clone responded only to MAP and the very closely related M. avium subspecies avium (MAA) while another responded to MAP, MAA and Mycobacterium intracellulare. A more broadly reactive T-cell clone reacted to MAP1508 which belongs to the esx protein family. CONCLUSIONS/SIGNIFICANCE:The presence of MAP reactive T cells with a Th1 or Th1/Th17 phenotype may suggest a possible role of mycobacteria in the inflammation seen in CD. The isolation of intestinal T cells followed by characterization of their specificity is a valuable tool to study the relative importance of different bacteria in CD.http://europepmc.org/articles/PMC2682569?pdf=render |
| spellingShingle | Ingrid Olsen Stig Tollefsen Claus Aagaard Liv J Reitan John P Bannantine Peter Andersen Ludvig M Sollid Knut E A Lundin Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients. PLoS ONE |
| title | Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients. |
| title_full | Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients. |
| title_fullStr | Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients. |
| title_full_unstemmed | Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients. |
| title_short | Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn's disease patients. |
| title_sort | isolation of mycobacterium avium subspecies paratuberculosis reactive cd4 t cells from intestinal biopsies of crohn s disease patients |
| url | http://europepmc.org/articles/PMC2682569?pdf=render |
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