Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens
The nature of effector cells and the potential immunogenicity of Leishmania major excreted/secreted proteins (LmES) were evaluated using peripheral blood mononuclear cells (PBMCs) from healed zoonotic cutaneous leishmaniasis individuals (HZCL) and healthy controls (HC). First, we found that PBMCs fr...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/636039 |
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| author | Ikbel Naouar Thouraya Boussoffara Melika Ben Ahmed Nabil Belhaj Hmida Adel Gharbi Sami Gritli Afif Ben Salah Hechmi Louzir |
| author_facet | Ikbel Naouar Thouraya Boussoffara Melika Ben Ahmed Nabil Belhaj Hmida Adel Gharbi Sami Gritli Afif Ben Salah Hechmi Louzir |
| author_sort | Ikbel Naouar |
| collection | DOAJ |
| description | The nature of effector cells and the potential immunogenicity of Leishmania major excreted/secreted proteins (LmES) were evaluated using peripheral blood mononuclear cells (PBMCs) from healed zoonotic cutaneous leishmaniasis individuals (HZCL) and healthy controls (HC). First, we found that PBMCs from HZCL individuals proliferate and produce high levels of IFN-γ and granzyme B (GrB), used as a marker of activated cytotoxic T cells, in response to the parasite antigens. IFN-γ is produced by CD4+ T cells, but unexpectedly GrB is also produced by CD4+ T cells in response to stimulation with LmES, which were found to be as effective as soluble Leishmania antigens to induce proliferation and cytokine production by PBMCs from immune individuals. To address the question of regulatory T cell (Tregs) involvement, the frequency of circulating Tregs was assessed and found to be higher in HZCL individuals compared to that of HC. Furthermore, both CD4+CD25+ and CD4+CD25− T cells, purified from HZCL individuals, produced IFN-γ and GrB when stimulated with LmES. Additional experiments showed that CD4+CD25+CD127dim/- Tregs were involved in GrB production. Collectively, our data indicate that LmES are immunogenic in humans and emphasize the involvement of CD4+ T cells including activated and regulatory T cells in the immune response against parasite antigens. |
| format | Article |
| id | doaj-art-1b27770cca3a4f04978017c6ee7c81d7 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1b27770cca3a4f04978017c6ee7c81d72025-02-03T06:01:39ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/636039636039Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major AntigensIkbel Naouar0Thouraya Boussoffara1Melika Ben Ahmed2Nabil Belhaj Hmida3Adel Gharbi4Sami Gritli5Afif Ben Salah6Hechmi Louzir7Laboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaLaboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaLaboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaLaboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaLaboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaDepartment of Pathology, Charles Nicolle Hospital, Boulevard 9 Avril 1938, 1006 Tunis, TunisiaLaboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaLaboratory of Transmission, Control, and Immunobiology of Infections-LR11IPT02, Pasteur Institute of Tunis, 13 Place Pasteur, 1002 Tunis, TunisiaThe nature of effector cells and the potential immunogenicity of Leishmania major excreted/secreted proteins (LmES) were evaluated using peripheral blood mononuclear cells (PBMCs) from healed zoonotic cutaneous leishmaniasis individuals (HZCL) and healthy controls (HC). First, we found that PBMCs from HZCL individuals proliferate and produce high levels of IFN-γ and granzyme B (GrB), used as a marker of activated cytotoxic T cells, in response to the parasite antigens. IFN-γ is produced by CD4+ T cells, but unexpectedly GrB is also produced by CD4+ T cells in response to stimulation with LmES, which were found to be as effective as soluble Leishmania antigens to induce proliferation and cytokine production by PBMCs from immune individuals. To address the question of regulatory T cell (Tregs) involvement, the frequency of circulating Tregs was assessed and found to be higher in HZCL individuals compared to that of HC. Furthermore, both CD4+CD25+ and CD4+CD25− T cells, purified from HZCL individuals, produced IFN-γ and GrB when stimulated with LmES. Additional experiments showed that CD4+CD25+CD127dim/- Tregs were involved in GrB production. Collectively, our data indicate that LmES are immunogenic in humans and emphasize the involvement of CD4+ T cells including activated and regulatory T cells in the immune response against parasite antigens.http://dx.doi.org/10.1155/2014/636039 |
| spellingShingle | Ikbel Naouar Thouraya Boussoffara Melika Ben Ahmed Nabil Belhaj Hmida Adel Gharbi Sami Gritli Afif Ben Salah Hechmi Louzir Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens Mediators of Inflammation |
| title | Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens |
| title_full | Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens |
| title_fullStr | Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens |
| title_full_unstemmed | Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens |
| title_short | Involvement of Different CD4+ T Cell Subsets Producing Granzyme B in the Immune Response to Leishmania major Antigens |
| title_sort | involvement of different cd4 t cell subsets producing granzyme b in the immune response to leishmania major antigens |
| url | http://dx.doi.org/10.1155/2014/636039 |
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