Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment.
The wide spectrum of clinical outcomes following infection with Mycobacterium tuberculosis is largely determined by the host immune response; therefore, we studied several clinically defined groups of individuals (n = 120) that differ in their ability to contain the bacillus. To quantitate M. tuberc...
| প্রধান লেখক: | , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
2001
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| _version_ | 1826273885730897920 |
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| author | Pathan, A Wilkinson, K Klenerman, P McShane, H Davidson, R Pasvol, G Hill, A Lalvani, A |
| author_facet | Pathan, A Wilkinson, K Klenerman, P McShane, H Davidson, R Pasvol, G Hill, A Lalvani, A |
| author_sort | Pathan, A |
| collection | OXFORD |
| description | The wide spectrum of clinical outcomes following infection with Mycobacterium tuberculosis is largely determined by the host immune response; therefore, we studied several clinically defined groups of individuals (n = 120) that differ in their ability to contain the bacillus. To quantitate M. tuberculosis-specific T cells directly ex vivo, we enumerated IFN-gamma-secreting CD4 T cells specific for ESAT-6, a secreted Ag that is highly specific for M. tuberculosis, and a target of protective immune responses in animal models. We found that frequencies of circulating ESAT-6 peptide-specific IFN-gamma-secreting CD4 T cells were higher in latently infected healthy contacts and subjects with minimal disease and low bacterial burdens than in patients with culture-positive active pulmonary tuberculosis (p = 0.009 and p = 0.002, respectively). Importantly, the frequency of these Ag-specific CD4 T cells fell progressively in all groups with treatment (p = 0.005), suggesting that the lower responses in patients with more extensive disease were not due to tuberculosis-induced immune suppression. This population of M. tuberculosis Ag-specific Th1-type CD4 T cells appears to correlate with clinical phenotype and declines during successful therapy; these features are consistent with a role for these T cells in the containment of M. tuberculosis in vivo. Such findings may assist in the design and evaluation of novel tuberculosis vaccine candidates. |
| first_indexed | 2024-03-06T22:35:02Z |
| format | Journal article |
| id | oxford-uuid:5998c60f-b07f-41fd-b4b1-fafab5ce5cf9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:35:02Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:5998c60f-b07f-41fd-b4b1-fafab5ce5cf92022-03-26T17:10:41ZDirect ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5998c60f-b07f-41fd-b4b1-fafab5ce5cf9EnglishSymplectic Elements at Oxford2001Pathan, AWilkinson, KKlenerman, PMcShane, HDavidson, RPasvol, GHill, ALalvani, AThe wide spectrum of clinical outcomes following infection with Mycobacterium tuberculosis is largely determined by the host immune response; therefore, we studied several clinically defined groups of individuals (n = 120) that differ in their ability to contain the bacillus. To quantitate M. tuberculosis-specific T cells directly ex vivo, we enumerated IFN-gamma-secreting CD4 T cells specific for ESAT-6, a secreted Ag that is highly specific for M. tuberculosis, and a target of protective immune responses in animal models. We found that frequencies of circulating ESAT-6 peptide-specific IFN-gamma-secreting CD4 T cells were higher in latently infected healthy contacts and subjects with minimal disease and low bacterial burdens than in patients with culture-positive active pulmonary tuberculosis (p = 0.009 and p = 0.002, respectively). Importantly, the frequency of these Ag-specific CD4 T cells fell progressively in all groups with treatment (p = 0.005), suggesting that the lower responses in patients with more extensive disease were not due to tuberculosis-induced immune suppression. This population of M. tuberculosis Ag-specific Th1-type CD4 T cells appears to correlate with clinical phenotype and declines during successful therapy; these features are consistent with a role for these T cells in the containment of M. tuberculosis in vivo. Such findings may assist in the design and evaluation of novel tuberculosis vaccine candidates. |
| spellingShingle | Pathan, A Wilkinson, K Klenerman, P McShane, H Davidson, R Pasvol, G Hill, A Lalvani, A Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. |
| title | Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. |
| title_full | Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. |
| title_fullStr | Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. |
| title_full_unstemmed | Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. |
| title_short | Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. |
| title_sort | direct ex vivo analysis of antigen specific ifn gamma secreting cd4 t cells in mycobacterium tuberculosis infected individuals associations with clinical disease state and effect of treatment |
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