Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis
Visceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti-Leishmania-specific CD4+ T-cell response, which is reversed after clinical cure. In contrast, th...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.773983/full |
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| author | Lorranny Santana Rodrigues Lorranny Santana Rodrigues Aline Silva Barreto Aline Silva Barreto Aline Silva Barreto Lays Gisele Santos Bomfim Lays Gisele Santos Bomfim Marcos Couto Gomes Nathalia Luisa Carlos Ferreira Geydson Silveira da Cruz Geydson Silveira da Cruz Lucas Sousa Magalhães Lucas Sousa Magalhães Amélia Ribeiro de Jesus Amélia Ribeiro de Jesus Amélia Ribeiro de Jesus Clarisa B. Palatnik-de-Sousa Clarisa B. Palatnik-de-Sousa Cristiane Bani Corrêa Cristiane Bani Corrêa Roque Pacheco de Almeida Roque Pacheco de Almeida Roque Pacheco de Almeida |
| author_facet | Lorranny Santana Rodrigues Lorranny Santana Rodrigues Aline Silva Barreto Aline Silva Barreto Aline Silva Barreto Lays Gisele Santos Bomfim Lays Gisele Santos Bomfim Marcos Couto Gomes Nathalia Luisa Carlos Ferreira Geydson Silveira da Cruz Geydson Silveira da Cruz Lucas Sousa Magalhães Lucas Sousa Magalhães Amélia Ribeiro de Jesus Amélia Ribeiro de Jesus Amélia Ribeiro de Jesus Clarisa B. Palatnik-de-Sousa Clarisa B. Palatnik-de-Sousa Cristiane Bani Corrêa Cristiane Bani Corrêa Roque Pacheco de Almeida Roque Pacheco de Almeida Roque Pacheco de Almeida |
| author_sort | Lorranny Santana Rodrigues |
| collection | DOAJ |
| description | Visceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti-Leishmania-specific CD4+ T-cell response, which is reversed after clinical cure. In contrast, the quality of the CD4+ and CD8+ T-cell responses involved in resistance and/or cure of VL relies on the capability of these cells to activate polyfunctional and memory responses, which are associated with the simultaneous production of three cytokines: IFN-γ, IL-2, and TNF-α. Models for the development of CD4 and CD8 T-cell quality in memory and protection to leishmaniasis have been described previously. We aimed to assess the functionality of the T cells involved in the recovery of the immune suppression throughout the VL treatment. Therefore, we cultured peripheral blood mononuclear cells (PBMCs) from VL patients and healthy controls in vitro with soluble Leishmania antigen (SLA). Cell surface markers and intracellular cytokine production were determined on days 7, 14, 21, 30, 60, 90, and 180 after the beginning of chemotherapy. We observed that the frequencies of CD4+TNF-α+IFN-γ+ and the multifunctional CD4+IL-2+TNF-α+IFN-γ+, together with CD4+TNF-α+ and CD4+IFN-γ+ T cells, increased throughout and at the end of the treatment, respectively. In addition, enhanced frequencies of CD8+IL-2+TNF-α+IFN-γ+ and CD8+TNF-α+IFN-γ T cells were also relevant in the healing process. Noteworthy, the frequencies of the CD4+ and CD8 central-memory T cells, which produce IL-2, TNF-α, and IFN-γ and ensure the memory response against parasite reinfection, are significantly enhanced in cured patients. In addition, the subset of the non-functional CD8Low population is predominant in VL untreated patients and decreases along the chemotherapy treatment. In contrast, a CD8High subset increased towards the cure. Furthermore, the cure due to treatment with meglumine antimoniate or with liposomal amphotericin B was associated with the recovery of the T-cell immune responses. We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4+ and CD8+ cytokine-secreting T cells. |
| first_indexed | 2024-12-19T02:57:05Z |
| format | Article |
| id | doaj.art-b71b1e0addeb432eb639111c3eaef850 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T02:57:05Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b71b1e0addeb432eb639111c3eaef8502022-12-21T20:38:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.773983773983Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral LeishmaniasisLorranny Santana Rodrigues0Lorranny Santana Rodrigues1Aline Silva Barreto2Aline Silva Barreto3Aline Silva Barreto4Lays Gisele Santos Bomfim5Lays Gisele Santos Bomfim6Marcos Couto Gomes7Nathalia Luisa Carlos Ferreira8Geydson Silveira da Cruz9Geydson Silveira da Cruz10Lucas Sousa Magalhães11Lucas Sousa Magalhães12Amélia Ribeiro de Jesus13Amélia Ribeiro de Jesus14Amélia Ribeiro de Jesus15Clarisa B. Palatnik-de-Sousa16Clarisa B. Palatnik-de-Sousa17Cristiane Bani Corrêa18Cristiane Bani Corrêa19Roque Pacheco de Almeida20Roque Pacheco de Almeida21Roque Pacheco de Almeida22Department of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDivision of Immunology and Molecular Biology Laboratory, University Hospital/Brazilian Hospital Services Company (EBSERH), Federal University of Sergipe, Sergipe, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDivision of Immunology and Molecular Biology Laboratory, University Hospital/Brazilian Hospital Services Company (EBSERH), Federal University of Sergipe, Sergipe, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDivision of Immunology and Molecular Biology Laboratory, University Hospital/Brazilian Hospital Services Company (EBSERH), Federal University of Sergipe, Sergipe, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilInstitute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Rio de Janeiro, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilLaboratory of Biology and Immunology of Cancer and Leishmania, Department of Morphology, Federal University of Sergipe, São Cristóvão, BrazilDepartment of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), National Insitute of Science and Technology (INCT), National Council for Scientific and Technological Development (CNPq), Aracaju, BrazilGraduate Program in Health Sciences, Federal University of Sergipe, Sergipe, BrazilDivision of Immunology and Molecular Biology Laboratory, University Hospital/Brazilian Hospital Services Company (EBSERH), Federal University of Sergipe, Sergipe, BrazilVisceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti-Leishmania-specific CD4+ T-cell response, which is reversed after clinical cure. In contrast, the quality of the CD4+ and CD8+ T-cell responses involved in resistance and/or cure of VL relies on the capability of these cells to activate polyfunctional and memory responses, which are associated with the simultaneous production of three cytokines: IFN-γ, IL-2, and TNF-α. Models for the development of CD4 and CD8 T-cell quality in memory and protection to leishmaniasis have been described previously. We aimed to assess the functionality of the T cells involved in the recovery of the immune suppression throughout the VL treatment. Therefore, we cultured peripheral blood mononuclear cells (PBMCs) from VL patients and healthy controls in vitro with soluble Leishmania antigen (SLA). Cell surface markers and intracellular cytokine production were determined on days 7, 14, 21, 30, 60, 90, and 180 after the beginning of chemotherapy. We observed that the frequencies of CD4+TNF-α+IFN-γ+ and the multifunctional CD4+IL-2+TNF-α+IFN-γ+, together with CD4+TNF-α+ and CD4+IFN-γ+ T cells, increased throughout and at the end of the treatment, respectively. In addition, enhanced frequencies of CD8+IL-2+TNF-α+IFN-γ+ and CD8+TNF-α+IFN-γ T cells were also relevant in the healing process. Noteworthy, the frequencies of the CD4+ and CD8 central-memory T cells, which produce IL-2, TNF-α, and IFN-γ and ensure the memory response against parasite reinfection, are significantly enhanced in cured patients. In addition, the subset of the non-functional CD8Low population is predominant in VL untreated patients and decreases along the chemotherapy treatment. In contrast, a CD8High subset increased towards the cure. Furthermore, the cure due to treatment with meglumine antimoniate or with liposomal amphotericin B was associated with the recovery of the T-cell immune responses. We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4+ and CD8+ cytokine-secreting T cells.https://www.frontiersin.org/articles/10.3389/fimmu.2021.773983/fullcellular immunityimmunophenotypingT-cell subsetsmultifunctionalhuman visceral leishmaniasisLeishmania (L.) infantum chagasi |
| spellingShingle | Lorranny Santana Rodrigues Lorranny Santana Rodrigues Aline Silva Barreto Aline Silva Barreto Aline Silva Barreto Lays Gisele Santos Bomfim Lays Gisele Santos Bomfim Marcos Couto Gomes Nathalia Luisa Carlos Ferreira Geydson Silveira da Cruz Geydson Silveira da Cruz Lucas Sousa Magalhães Lucas Sousa Magalhães Amélia Ribeiro de Jesus Amélia Ribeiro de Jesus Amélia Ribeiro de Jesus Clarisa B. Palatnik-de-Sousa Clarisa B. Palatnik-de-Sousa Cristiane Bani Corrêa Cristiane Bani Corrêa Roque Pacheco de Almeida Roque Pacheco de Almeida Roque Pacheco de Almeida Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis Frontiers in Immunology cellular immunity immunophenotyping T-cell subsets multifunctional human visceral leishmaniasis Leishmania (L.) infantum chagasi |
| title | Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis |
| title_full | Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis |
| title_fullStr | Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis |
| title_full_unstemmed | Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis |
| title_short | Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis |
| title_sort | multifunctional tnf α and ifn γ secreting cd4 and cd8 t cells and cd8high t cells are associated with the cure of human visceral leishmaniasis |
| topic | cellular immunity immunophenotyping T-cell subsets multifunctional human visceral leishmaniasis Leishmania (L.) infantum chagasi |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.773983/full |
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