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In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response
In recent years, the impact of antituberculous treatment on interferon (IFN)-gamma response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-gamma response...
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| Published in: | PloS one 2009-04, Vol.4 (4), p.e5187-e5187 |
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| creator | Sauzullo, Ilaria Mengoni, Fabio Lichtner, Miriam Massetti, Anna Paola Rossi, Raffaella Iannetta, Marco Marocco, Raffaella Del Borgo, Cosmo Soscia, Fabrizio Vullo, Vincenzo Mastroianni, Claudio Maria |
| description | In recent years, the impact of antituberculous treatment on interferon (IFN)-gamma response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-gamma response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-gamma.
38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-gamma is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-gamma production within the range of therapeutically achievable concentrations.
The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response. |
| doi_str_mv | 10.1371/journal.pone.0005187 |
| format | article |
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38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-gamma is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-gamma production within the range of therapeutically achievable concentrations.
The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005187</identifier><identifier>PMID: 19365543</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Aged ; Antigens ; Antigens, Bacterial - immunology ; Antitubercular Agents - immunology ; Antitubercular Agents - therapeutic use ; Blood & organ donations ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - secretion ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - secretion ; Clinical medicine ; Drugs ; Effector cells ; ESAT-6 antigen ; Female ; Humans ; Immunological memory ; Incubation ; Infections ; Infectious Diseases ; Infectious Diseases/Bacterial Infections ; Infectious Diseases/Respiratory Infections ; Interferon ; Interferon-gamma - immunology ; Interferon-gamma - secretion ; Lymphocytes ; Lymphocytes T ; Male ; Memory cells ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Patients ; Pharmacology ; Reversion ; Skin ; T cell receptors ; Therapy ; Tropical diseases ; Tuberculosis ; Tuberculosis - drug therapy ; Tuberculosis - immunology ; Young Adult ; γ-Interferon</subject><ispartof>PloS one, 2009-04, Vol.4 (4), p.e5187-e5187</ispartof><rights>2009 Sauzullo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Sauzullo et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-6f9dbc5668e63caebe9c59e9a285d633c0bdcc7b52bf1cd3eb79414e9f1f2dc53</citedby><cites>FETCH-LOGICAL-c524t-6f9dbc5668e63caebe9c59e9a285d633c0bdcc7b52bf1cd3eb79414e9f1f2dc53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1290548274/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1290548274?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,37048,44625,53827,53829,75483</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19365543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Maartens, Gary</contributor><creatorcontrib>Sauzullo, Ilaria</creatorcontrib><creatorcontrib>Mengoni, Fabio</creatorcontrib><creatorcontrib>Lichtner, Miriam</creatorcontrib><creatorcontrib>Massetti, Anna Paola</creatorcontrib><creatorcontrib>Rossi, Raffaella</creatorcontrib><creatorcontrib>Iannetta, Marco</creatorcontrib><creatorcontrib>Marocco, Raffaella</creatorcontrib><creatorcontrib>Del Borgo, Cosmo</creatorcontrib><creatorcontrib>Soscia, Fabrizio</creatorcontrib><creatorcontrib>Vullo, Vincenzo</creatorcontrib><creatorcontrib>Mastroianni, Claudio Maria</creatorcontrib><title>In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In recent years, the impact of antituberculous treatment on interferon (IFN)-gamma response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-gamma response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-gamma.
38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-gamma is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-gamma production within the range of therapeutically achievable concentrations.
The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antigens</subject><subject>Antigens, Bacterial - immunology</subject><subject>Antitubercular Agents - immunology</subject><subject>Antitubercular Agents - therapeutic use</subject><subject>Blood & organ donations</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - secretion</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - secretion</subject><subject>Clinical medicine</subject><subject>Drugs</subject><subject>Effector cells</subject><subject>ESAT-6 antigen</subject><subject>Female</subject><subject>Humans</subject><subject>Immunological memory</subject><subject>Incubation</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Infectious Diseases/Bacterial Infections</subject><subject>Infectious Diseases/Respiratory Infections</subject><subject>Interferon</subject><subject>Interferon-gamma - immunology</subject><subject>Interferon-gamma - secretion</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Memory cells</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Patients</subject><subject>Pharmacology</subject><subject>Reversion</subject><subject>Skin</subject><subject>T cell receptors</subject><subject>Therapy</subject><subject>Tropical diseases</subject><subject>Tuberculosis</subject><subject>Tuberculosis - drug therapy</subject><subject>Tuberculosis - immunology</subject><subject>Young Adult</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUtuK1EAQDaK4u6N_INog-JYxfU36RZBF14EFX9bnpi_VY4YkPXZ3Bvbv7ThRd8WnKqrOOXXhVNUr3GwxbfH7Q5jjpIftMUywbZqG4659Ul1iSUktSEOfPsgvqquUDgVDOyGeVxelIThn9LIadhM69aeA9ORQv-Q5BgTeg80JBV_quc-zgWjnIaQ-oRxB5xGmjMKExnsbjLYZYq-Hwi-Jhximeq_HUaM7ZGEYUIRUtkzwonrm9ZDg5Ro31bfPn-6uv9S3X2921x9va8sJy7Xw0hnLhehAUKvBgLRcgtSk405QahvjrG0NJ8Zj6yiYVjLMQHrsibOcbqo3Z91jWVmtj0oKE9lw1pGWFcTujHBBH9Qx9qOO9yroXv0qhLhXOubeDqBs6zRzXnaSamal7bQzREjp22U8x0XrwzptNiM4W14T9fBI9HFn6r-rfTgpIgRj5Z5N9W4ViOHHDCmrsU_L4_QEYU5KtJh0mLQF-PYf4P9vY2eUjSGlCP7PKrhRi3V-s9RiHbVap9BePzzjL2n1Cv0Jg6zF0A</recordid><startdate>20090413</startdate><enddate>20090413</enddate><creator>Sauzullo, Ilaria</creator><creator>Mengoni, Fabio</creator><creator>Lichtner, Miriam</creator><creator>Massetti, Anna Paola</creator><creator>Rossi, Raffaella</creator><creator>Iannetta, Marco</creator><creator>Marocco, Raffaella</creator><creator>Del Borgo, Cosmo</creator><creator>Soscia, Fabrizio</creator><creator>Vullo, Vincenzo</creator><creator>Mastroianni, Claudio Maria</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090413</creationdate><title>In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response</title><author>Sauzullo, Ilaria ; Mengoni, Fabio ; Lichtner, Miriam ; Massetti, Anna Paola ; Rossi, Raffaella ; Iannetta, Marco ; Marocco, Raffaella ; Del Borgo, Cosmo ; Soscia, Fabrizio ; Vullo, Vincenzo ; Mastroianni, Claudio Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c524t-6f9dbc5668e63caebe9c59e9a285d633c0bdcc7b52bf1cd3eb79414e9f1f2dc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antigens</topic><topic>Antigens, Bacterial - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sauzullo, Ilaria</au><au>Mengoni, Fabio</au><au>Lichtner, Miriam</au><au>Massetti, Anna Paola</au><au>Rossi, Raffaella</au><au>Iannetta, Marco</au><au>Marocco, Raffaella</au><au>Del Borgo, Cosmo</au><au>Soscia, Fabrizio</au><au>Vullo, Vincenzo</au><au>Mastroianni, Claudio Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-04-13</date><risdate>2009</risdate><volume>4</volume><issue>4</issue><spage>e5187</spage><epage>e5187</epage><pages>e5187-e5187</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Conceived and designed the experiments: IS FM CMM. Performed the experiments: IS FM RR RM. Analyzed the data: IS FM ML APM. Contributed reagents/materials/analysis tools: VV CMM. Wrote the paper: IS FM VV CMM. Contributed to the enrollment of patients: MI CDB VV FS.</notes><abstract>In recent years, the impact of antituberculous treatment on interferon (IFN)-gamma response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-gamma response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-gamma.
38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-gamma is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-gamma production within the range of therapeutically achievable concentrations.
The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19365543</pmid><doi>10.1371/journal.pone.0005187</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-04, Vol.4 (4), p.e5187-e5187 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1290548274 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | Adolescent Adult Aged Antigens Antigens, Bacterial - immunology Antitubercular Agents - immunology Antitubercular Agents - therapeutic use Blood & organ donations CD4 antigen CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - secretion CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - secretion Clinical medicine Drugs Effector cells ESAT-6 antigen Female Humans Immunological memory Incubation Infections Infectious Diseases Infectious Diseases/Bacterial Infections Infectious Diseases/Respiratory Infections Interferon Interferon-gamma - immunology Interferon-gamma - secretion Lymphocytes Lymphocytes T Male Memory cells Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Patients Pharmacology Reversion Skin T cell receptors Therapy Tropical diseases Tuberculosis Tuberculosis - drug therapy Tuberculosis - immunology Young Adult γ-Interferon |
| title | In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T16%3A57%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20vivo%20and%20in%20vitro%20effects%20of%20antituberculosis%20treatment%20on%20mycobacterial%20interferon-gamma%20T%20cell%20response&rft.jtitle=PloS%20one&rft.au=Sauzullo,%20Ilaria&rft.date=2009-04-13&rft.volume=4&rft.issue=4&rft.spage=e5187&rft.epage=e5187&rft.pages=e5187-e5187&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0005187&rft_dat=%3Cproquest_plos_%3E2897411761%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c524t-6f9dbc5668e63caebe9c59e9a285d633c0bdcc7b52bf1cd3eb79414e9f1f2dc53%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1290548274&rft_id=info:pmid/19365543&rfr_iscdi=true |