Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load.
Distinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in...
| Autors principals: | , , , , , , , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
2007
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| _version_ | 1826265176682266624 |
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| author | Millington, K Innes, J Hackforth, S Hinks, T Deeks, J Dosanjh, D Guyot-Revol, V Gunatheesan, R Klenerman, P Lalvani, A |
| author_facet | Millington, K Innes, J Hackforth, S Hinks, T Deeks, J Dosanjh, D Guyot-Revol, V Gunatheesan, R Klenerman, P Lalvani, A |
| author_sort | Millington, K |
| collection | OXFORD |
| description | Distinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis when bacterial and Ag loads are high and after curative treatment, when Ag load is reduced. The frequencies of M. tuberculosis Ag-specific IFN-gamma-secreting T cells declined during 28 mo of follow-up with an average percentage decline of 5.8% per year (p = 0.005), while the frequencies of Ag-specific IL-2-secreting T cells increased during treatment (p = 0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma- and IL-2-secreting cells over 28 mo. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single-cell level revealed a codominance of IFN-gamma-only secreting and IFN-gamma/IL-2 dual secreting CD4(+) T cells in active disease that shifted to dominance of IFN-gamma/IL-2-secreting CD4(+) T cells and newly detectable IL-2-only secreting CD4(+) T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis that now requires validation in larger prospective studies. |
| first_indexed | 2024-03-06T20:19:32Z |
| format | Journal article |
| id | oxford-uuid:2d5094e7-39f8-4d8c-aee8-a0248e9d5d04 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:19:32Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:2d5094e7-39f8-4d8c-aee8-a0248e9d5d042022-03-26T12:42:11ZDynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2d5094e7-39f8-4d8c-aee8-a0248e9d5d04EnglishSymplectic Elements at Oxford2007Millington, KInnes, JHackforth, SHinks, TDeeks, JDosanjh, DGuyot-Revol, VGunatheesan, RKlenerman, PLalvani, ADistinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis when bacterial and Ag loads are high and after curative treatment, when Ag load is reduced. The frequencies of M. tuberculosis Ag-specific IFN-gamma-secreting T cells declined during 28 mo of follow-up with an average percentage decline of 5.8% per year (p = 0.005), while the frequencies of Ag-specific IL-2-secreting T cells increased during treatment (p = 0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma- and IL-2-secreting cells over 28 mo. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single-cell level revealed a codominance of IFN-gamma-only secreting and IFN-gamma/IL-2 dual secreting CD4(+) T cells in active disease that shifted to dominance of IFN-gamma/IL-2-secreting CD4(+) T cells and newly detectable IL-2-only secreting CD4(+) T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis that now requires validation in larger prospective studies. |
| spellingShingle | Millington, K Innes, J Hackforth, S Hinks, T Deeks, J Dosanjh, D Guyot-Revol, V Gunatheesan, R Klenerman, P Lalvani, A Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. |
| title | Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. |
| title_full | Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. |
| title_fullStr | Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. |
| title_full_unstemmed | Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. |
| title_short | Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. |
| title_sort | dynamic relationship between ifn gamma and il 2 profile of mycobacterium tuberculosis specific t cells and antigen load |
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