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Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis

The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular...

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Autores principales: Egui, Adriana, Ledesma, Darién, Pérez-Antón, Elena, Montoya, Andrés, Gómez, Inmaculada, Robledo, Sara María, Infante, Juan José, Vélez, Ivan Darío, López, Manuel C., Thomas, M. Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252334/
https://www.ncbi.nlm.nih.gov/pubmed/30510917
http://dx.doi.org/10.3389/fcimb.2018.00393
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author Egui, Adriana
Ledesma, Darién
Pérez-Antón, Elena
Montoya, Andrés
Gómez, Inmaculada
Robledo, Sara María
Infante, Juan José
Vélez, Ivan Darío
López, Manuel C.
Thomas, M. Carmen
author_facet Egui, Adriana
Ledesma, Darién
Pérez-Antón, Elena
Montoya, Andrés
Gómez, Inmaculada
Robledo, Sara María
Infante, Juan José
Vélez, Ivan Darío
López, Manuel C.
Thomas, M. Carmen
author_sort Egui, Adriana
collection PubMed
description The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response. The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4(+) and CD8(+) T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD). Peripheral blood mononuclear cells (PBMCs) from the patients exhibited a lymphoproliferative capacity after stimulation with total soluble protein from either Leishmania panamensis (SLpA) or Leishmania infantum (SLiA) or with a recombinant paraflagellar rod protein-1 (rPFR1). Higher frequencies of antigen-specific T(NAIVE) cells, mainly following stimulation with rPFR1, were observed in asymptomatic and cured patients than in patients with active cutaneous leishmaniasis, while T cells from patients with active cutaneous leishmaniasis showed a higher percentage of effector memory T cells (T(EM) for CD4(+) T cells and T(EMRA) for CD8(+) T cells). The amount of antigen-specific CD57(+)/CD8(+) T(EMRA) cells in patients with active cutaneous leishmaniasis was higher than that in cured patients and asymptomatic subjects. Regarding functionality, a more robust multifunctional CD8(+) T cell response was detected in cured patients than in those with active cutaneous leishmaniasis. Moreover, cured patients showed a significant increase in the frequency of cells expressing a Th1-type cytotoxic production profile (IFN-γ(+)/granzyme-B/(+)perforin(+)). Patients with an active leishmaniosis process had a significantly higher frequency of CD8(+) T cells expressing the inhibitory CD160 and 2B4 receptors than did cured patients. The expression profile observed in cured patients could be indicative of an imbalance toward a CD8(+) Th1 response, which could be associated with infection control; consequently, the determination of this profile could be a useful tool for facilitating the clinical follow-up of patients with cutaneous leishmaniasis. The results also suggest a possible exhaustion process of CD8(+) T cells associated with the evolution of Leishmania infection.
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spelling pubmed-62523342018-12-03 Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis Egui, Adriana Ledesma, Darién Pérez-Antón, Elena Montoya, Andrés Gómez, Inmaculada Robledo, Sara María Infante, Juan José Vélez, Ivan Darío López, Manuel C. Thomas, M. Carmen Front Cell Infect Microbiol Cellular and Infection Microbiology The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response. The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4(+) and CD8(+) T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD). Peripheral blood mononuclear cells (PBMCs) from the patients exhibited a lymphoproliferative capacity after stimulation with total soluble protein from either Leishmania panamensis (SLpA) or Leishmania infantum (SLiA) or with a recombinant paraflagellar rod protein-1 (rPFR1). Higher frequencies of antigen-specific T(NAIVE) cells, mainly following stimulation with rPFR1, were observed in asymptomatic and cured patients than in patients with active cutaneous leishmaniasis, while T cells from patients with active cutaneous leishmaniasis showed a higher percentage of effector memory T cells (T(EM) for CD4(+) T cells and T(EMRA) for CD8(+) T cells). The amount of antigen-specific CD57(+)/CD8(+) T(EMRA) cells in patients with active cutaneous leishmaniasis was higher than that in cured patients and asymptomatic subjects. Regarding functionality, a more robust multifunctional CD8(+) T cell response was detected in cured patients than in those with active cutaneous leishmaniasis. Moreover, cured patients showed a significant increase in the frequency of cells expressing a Th1-type cytotoxic production profile (IFN-γ(+)/granzyme-B/(+)perforin(+)). Patients with an active leishmaniosis process had a significantly higher frequency of CD8(+) T cells expressing the inhibitory CD160 and 2B4 receptors than did cured patients. The expression profile observed in cured patients could be indicative of an imbalance toward a CD8(+) Th1 response, which could be associated with infection control; consequently, the determination of this profile could be a useful tool for facilitating the clinical follow-up of patients with cutaneous leishmaniasis. The results also suggest a possible exhaustion process of CD8(+) T cells associated with the evolution of Leishmania infection. Frontiers Media S.A. 2018-11-19 /pmc/articles/PMC6252334/ /pubmed/30510917 http://dx.doi.org/10.3389/fcimb.2018.00393 Text en Copyright © 2018 Egui, Ledesma, Pérez-Antón, Montoya, Gómez, Robledo, Infante, Vélez, López and Thomas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Egui, Adriana
Ledesma, Darién
Pérez-Antón, Elena
Montoya, Andrés
Gómez, Inmaculada
Robledo, Sara María
Infante, Juan José
Vélez, Ivan Darío
López, Manuel C.
Thomas, M. Carmen
Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
title Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
title_full Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
title_fullStr Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
title_full_unstemmed Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
title_short Phenotypic and Functional Profiles of Antigen-Specific CD4(+) and CD8(+) T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
title_sort phenotypic and functional profiles of antigen-specific cd4(+) and cd8(+) t cells associated with infection control in patients with cutaneous leishmaniasis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252334/
https://www.ncbi.nlm.nih.gov/pubmed/30510917
http://dx.doi.org/10.3389/fcimb.2018.00393
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