Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients
Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correl...
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| Veröffentlicht in: | Parasite immunology 2000-02, Vol.22 (2), p.73-79 |
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| creator | Cabrera, Maira M.blackwell, Jenefer Castes, Marianella Trujillo, Dinorah Convit, Jacinto Shaw, Marie‐Anne |
| description | Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)‐γ and interleukin (IL)‐5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL‐5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN‐γ responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN‐γ responses to BCG. Treatment enhanced the IFN‐γ response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN‐γ responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL‐5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL‐5 levels. There were no significant changes in serum IL‐5 with treatment. Overall results show enhanced antigen‐specific IFN‐γ responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN‐γ. |
| doi_str_mv | 10.1046/j.1365-3024.2000.00278.x |
| format | Article |
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The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)‐γ and interleukin (IL)‐5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL‐5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN‐γ responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN‐γ responses to BCG. Treatment enhanced the IFN‐γ response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN‐γ responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL‐5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL‐5 levels. There were no significant changes in serum IL‐5 with treatment. Overall results show enhanced antigen‐specific IFN‐γ responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN‐γ.</description><identifier>ISSN: 0141-9838</identifier><identifier>EISSN: 1365-3024</identifier><identifier>DOI: 10.1046/j.1365-3024.2000.00278.x</identifier><identifier>PMID: 10652119</identifier><language>eng</language><publisher>Oxford, U.K. and Cambridge, USA: Blackwell Science Ltd</publisher><subject>Adolescent ; Adult ; AIDS/HIV ; Animals ; Antiprotozoal Agents - therapeutic use ; BCG ; BCG Vaccine - therapeutic use ; Cell Division ; Combined Modality Therapy ; Cutaneous leishmaniasis ; Female ; Humans ; Immunity, Cellular ; immunotherapy ; Interferon-gamma - blood ; Interleukin-5 - blood ; Leishmania - immunology ; Leishmania amazonensis ; Leishmaniasis, Cutaneous - blood ; Leishmaniasis, Cutaneous - immunology ; Leishmaniasis, Cutaneous - therapy ; Leishmaniasis, Mucocutaneous - blood ; Leishmaniasis, Mucocutaneous - immunology ; Leishmaniasis, Mucocutaneous - therapy ; Lymphocyte Activation ; Male ; Meglumine - therapeutic use ; Middle Aged ; Mycobacterium bovis - immunology ; Organometallic Compounds - therapeutic use ; Protozoan Vaccines - pharmacology ; Protozoan Vaccines - therapeutic use ; T-Lymphocytes, Helper-Inducer - immunology ; Th1 Cells - immunology ; Tuberculin - pharmacology ; Tuberculin - therapeutic use</subject><ispartof>Parasite immunology, 2000-02, Vol.22 (2), p.73-79</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3958-b7a2ef5421d96b569a04487106e8b4498ec0768adee04f7f4b126c89df2bf11c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-3024.2000.00278.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-3024.2000.00278.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27923,27924,45573,45574,46408,46832</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10652119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cabrera, Maira</creatorcontrib><creatorcontrib>M.blackwell, Jenefer</creatorcontrib><creatorcontrib>Castes, Marianella</creatorcontrib><creatorcontrib>Trujillo, Dinorah</creatorcontrib><creatorcontrib>Convit, Jacinto</creatorcontrib><creatorcontrib>Shaw, Marie‐Anne</creatorcontrib><title>Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients</title><title>Parasite immunology</title><addtitle>Parasite Immunol</addtitle><description>Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)‐γ and interleukin (IL)‐5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL‐5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN‐γ responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN‐γ responses to BCG. Treatment enhanced the IFN‐γ response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN‐γ responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL‐5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL‐5 levels. There were no significant changes in serum IL‐5 with treatment. Overall results show enhanced antigen‐specific IFN‐γ responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN‐γ.</description><subject>Adolescent</subject><subject>Adult</subject><subject>AIDS/HIV</subject><subject>Animals</subject><subject>Antiprotozoal Agents - therapeutic use</subject><subject>BCG</subject><subject>BCG Vaccine - therapeutic use</subject><subject>Cell Division</subject><subject>Combined Modality Therapy</subject><subject>Cutaneous leishmaniasis</subject><subject>Female</subject><subject>Humans</subject><subject>Immunity, Cellular</subject><subject>immunotherapy</subject><subject>Interferon-gamma - blood</subject><subject>Interleukin-5 - blood</subject><subject>Leishmania - immunology</subject><subject>Leishmania amazonensis</subject><subject>Leishmaniasis, Cutaneous - blood</subject><subject>Leishmaniasis, Cutaneous - immunology</subject><subject>Leishmaniasis, Cutaneous - therapy</subject><subject>Leishmaniasis, Mucocutaneous - blood</subject><subject>Leishmaniasis, Mucocutaneous - immunology</subject><subject>Leishmaniasis, Mucocutaneous - therapy</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>Meglumine - therapeutic use</subject><subject>Middle Aged</subject><subject>Mycobacterium bovis - immunology</subject><subject>Organometallic Compounds - therapeutic use</subject><subject>Protozoan Vaccines - pharmacology</subject><subject>Protozoan Vaccines - therapeutic use</subject><subject>T-Lymphocytes, Helper-Inducer - immunology</subject><subject>Th1 Cells - immunology</subject><subject>Tuberculin - pharmacology</subject><subject>Tuberculin - therapeutic use</subject><issn>0141-9838</issn><issn>1365-3024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAURi1ERYfCKyCv2CXc6ziJI7EpI2hHGtQuytpynBuNp84PcUI7O7bseMY-CRlSVezo6lq65_ts6zDGEWIEmX3Yx5hkaZSAkLEAgBhA5Cq-f8FWT4uXbAUoMSpUok7Z6xD2AJiILHnFThGyVCAWK_Zr0zRT2407Gkx_4Hdu3HHvfhD_tL7gvZ8C35EZ-a3zniq-JRd2jWmd4a6tJkuBG34zI76ngePDz9_e3RIfKPRdG2iG-HlDg7Om5XYaTUvd3OifWoILvDejo3YMb9hJbXygt4_zjH378vlmfRltry426_NtZJMiVVGZG0F1KgVWRVamWWFASpXPPyJVSlkospBnylREIOu8liWKzKqiqkVZI9rkjL1fevuh-z5RGHXjgiXvl9fpHFSupJT_BTFPATFNZ1AtoB26EAaqdT-4xgwHjaCPvvReH7XooxZ99KX_-tL3c_Td4x1T2VD1T3ARNAMfF-DOeTo8u1hfb77Oh-QPdHumOw</recordid><startdate>200002</startdate><enddate>200002</enddate><creator>Cabrera, Maira</creator><creator>M.blackwell, Jenefer</creator><creator>Castes, Marianella</creator><creator>Trujillo, Dinorah</creator><creator>Convit, Jacinto</creator><creator>Shaw, Marie‐Anne</creator><general>Blackwell Science Ltd</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>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>200002</creationdate><title>Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients</title><author>Cabrera, Maira ; M.blackwell, Jenefer ; Castes, Marianella ; Trujillo, Dinorah ; Convit, Jacinto ; Shaw, Marie‐Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3958-b7a2ef5421d96b569a04487106e8b4498ec0768adee04f7f4b126c89df2bf11c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>AIDS/HIV</topic><topic>Animals</topic><topic>Antiprotozoal Agents - therapeutic use</topic><topic>BCG</topic><topic>BCG Vaccine - therapeutic use</topic><topic>Cell Division</topic><topic>Combined Modality Therapy</topic><topic>Cutaneous leishmaniasis</topic><topic>Female</topic><topic>Humans</topic><topic>Immunity, Cellular</topic><topic>immunotherapy</topic><topic>Interferon-gamma - blood</topic><topic>Interleukin-5 - blood</topic><topic>Leishmania - immunology</topic><topic>Leishmania amazonensis</topic><topic>Leishmaniasis, Cutaneous - blood</topic><topic>Leishmaniasis, Cutaneous - immunology</topic><topic>Leishmaniasis, Cutaneous - therapy</topic><topic>Leishmaniasis, Mucocutaneous - blood</topic><topic>Leishmaniasis, Mucocutaneous - immunology</topic><topic>Leishmaniasis, Mucocutaneous - therapy</topic><topic>Lymphocyte Activation</topic><topic>Male</topic><topic>Meglumine - therapeutic use</topic><topic>Middle Aged</topic><topic>Mycobacterium bovis - immunology</topic><topic>Organometallic Compounds - therapeutic use</topic><topic>Protozoan Vaccines - pharmacology</topic><topic>Protozoan Vaccines - therapeutic use</topic><topic>T-Lymphocytes, Helper-Inducer - immunology</topic><topic>Th1 Cells - immunology</topic><topic>Tuberculin - pharmacology</topic><topic>Tuberculin - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cabrera, Maira</creatorcontrib><creatorcontrib>M.blackwell, Jenefer</creatorcontrib><creatorcontrib>Castes, Marianella</creatorcontrib><creatorcontrib>Trujillo, Dinorah</creatorcontrib><creatorcontrib>Convit, Jacinto</creatorcontrib><creatorcontrib>Shaw, Marie‐Anne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Parasite immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cabrera, Maira</au><au>M.blackwell, Jenefer</au><au>Castes, Marianella</au><au>Trujillo, Dinorah</au><au>Convit, Jacinto</au><au>Shaw, Marie‐Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients</atitle><jtitle>Parasite immunology</jtitle><addtitle>Parasite Immunol</addtitle><date>2000-02</date><risdate>2000</risdate><volume>22</volume><issue>2</issue><spage>73</spage><epage>79</epage><pages>73-79</pages><issn>0141-9838</issn><eissn>1365-3024</eissn><abstract>Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)‐γ and interleukin (IL)‐5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL‐5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN‐γ responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN‐γ responses to BCG. Treatment enhanced the IFN‐γ response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN‐γ responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL‐5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL‐5 levels. There were no significant changes in serum IL‐5 with treatment. Overall results show enhanced antigen‐specific IFN‐γ responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN‐γ.</abstract><cop>Oxford, U.K. and Cambridge, USA</cop><pub>Blackwell Science Ltd</pub><pmid>10652119</pmid><doi>10.1046/j.1365-3024.2000.00278.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Adolescent Adult AIDS/HIV Animals Antiprotozoal Agents - therapeutic use BCG BCG Vaccine - therapeutic use Cell Division Combined Modality Therapy Cutaneous leishmaniasis Female Humans Immunity, Cellular immunotherapy Interferon-gamma - blood Interleukin-5 - blood Leishmania - immunology Leishmania amazonensis Leishmaniasis, Cutaneous - blood Leishmaniasis, Cutaneous - immunology Leishmaniasis, Cutaneous - therapy Leishmaniasis, Mucocutaneous - blood Leishmaniasis, Mucocutaneous - immunology Leishmaniasis, Mucocutaneous - therapy Lymphocyte Activation Male Meglumine - therapeutic use Middle Aged Mycobacterium bovis - immunology Organometallic Compounds - therapeutic use Protozoan Vaccines - pharmacology Protozoan Vaccines - therapeutic use T-Lymphocytes, Helper-Inducer - immunology Th1 Cells - immunology Tuberculin - pharmacology Tuberculin - therapeutic use |
| title | Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients |
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