Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment.
RATIONALE:Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3852504?pdf=render |
| _version_ | 1818319960608342016 |
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| author | Melissa R Nyendak Byung Park Megan D Null Joy Baseke Gwendolyn Swarbrick Harriet Mayanja-Kizza Mary Nsereko Denise F Johnson Phineas Gitta Alphonse Okwera Stefan Goldberg Lorna Bozeman John L Johnson W Henry Boom Deborah A Lewinsohn David M Lewinsohn Tuberculosis Research Unit and the Tuberculosis Trials Consortium |
| author_facet | Melissa R Nyendak Byung Park Megan D Null Joy Baseke Gwendolyn Swarbrick Harriet Mayanja-Kizza Mary Nsereko Denise F Johnson Phineas Gitta Alphonse Okwera Stefan Goldberg Lorna Bozeman John L Johnson W Henry Boom Deborah A Lewinsohn David M Lewinsohn Tuberculosis Research Unit and the Tuberculosis Trials Consortium |
| author_sort | Melissa R Nyendak |
| collection | DOAJ |
| description | RATIONALE:Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. OBJECTIVES:We sought to determine the relationship of Mtb specific CD4(+) T cells and CD8(+) T cells with duration of antituberculosis treatment. MATERIALS AND METHODS:We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4(+) and CD8(+) T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24. RESULTS:There was a significant difference in the Mtb specific CD8(+) T response, but not the CD4(+) T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8(+) T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4(+) T cell during the treatment. The Mtb specific CD4(+) T cell response, but not the CD8(+) response, was negatively impacted by the body mass index. CONCLUSIONS:Our data provide evidence that the Mtb specific CD8(+) T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8(+) T cell response can detect early treatment failure, relapse, or to predict disease progression. |
| first_indexed | 2024-12-13T10:17:25Z |
| format | Article |
| id | doaj.art-3f1e8df2bfa044d58cd5140c888c64a6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:17:25Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3f1e8df2bfa044d58cd5140c888c64a62022-12-21T23:51:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8156410.1371/journal.pone.0081564Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment.Melissa R NyendakByung ParkMegan D NullJoy BasekeGwendolyn SwarbrickHarriet Mayanja-KizzaMary NserekoDenise F JohnsonPhineas GittaAlphonse OkweraStefan GoldbergLorna BozemanJohn L JohnsonW Henry BoomDeborah A LewinsohnDavid M LewinsohnTuberculosis Research Unit and the Tuberculosis Trials ConsortiumRATIONALE:Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. OBJECTIVES:We sought to determine the relationship of Mtb specific CD4(+) T cells and CD8(+) T cells with duration of antituberculosis treatment. MATERIALS AND METHODS:We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4(+) and CD8(+) T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24. RESULTS:There was a significant difference in the Mtb specific CD8(+) T response, but not the CD4(+) T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8(+) T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4(+) T cell during the treatment. The Mtb specific CD4(+) T cell response, but not the CD8(+) response, was negatively impacted by the body mass index. CONCLUSIONS:Our data provide evidence that the Mtb specific CD8(+) T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8(+) T cell response can detect early treatment failure, relapse, or to predict disease progression.http://europepmc.org/articles/PMC3852504?pdf=render |
| spellingShingle | Melissa R Nyendak Byung Park Megan D Null Joy Baseke Gwendolyn Swarbrick Harriet Mayanja-Kizza Mary Nsereko Denise F Johnson Phineas Gitta Alphonse Okwera Stefan Goldberg Lorna Bozeman John L Johnson W Henry Boom Deborah A Lewinsohn David M Lewinsohn Tuberculosis Research Unit and the Tuberculosis Trials Consortium Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. PLoS ONE |
| title | Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. |
| title_full | Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. |
| title_fullStr | Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. |
| title_full_unstemmed | Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. |
| title_short | Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment. |
| title_sort | mycobacterium tuberculosis specific cd8 t cells rapidly decline with antituberculosis treatment |
| url | http://europepmc.org/articles/PMC3852504?pdf=render |
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