Phenotypic and Functional Profiles of Antigen-Specific CD4+ and CD8+ T Cells Associated With Infection Control in Patients With Cutaneous Leishmaniasis
| Autor: | Darién Ledesma, Juan José Infante, Andrés Eduardo Toro Montoya, Adriana Egui, Elena Pérez-Antón, M. Carmen Thomas, Sara M. Robledo, Manuel Carlos López, Iván D. Vélez, Inmaculada Gómez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes paraflagellar rod protein-1 lcsh:QR1-502 Protozoan Proteins CD8-Positive T-Lymphocytes lcsh:Microbiology Granzymes 0302 clinical medicine Cellular and Infection Microbiology CD57 Antigens Cytotoxic T cell Leishmania infantum Receptors Immunologic CD8+ and CD4+ T-cells Original Research Leishmania biology Recombinant Proteins Infectious Diseases CD4 Antigens Cytokines Microbiology (medical) phenotype 030231 tropical medicine Immunology Leishmaniasis Cutaneous Antigens Protozoan GPI-Linked Proteins Microbiology 03 medical and health sciences Interferon-gamma Immune system Cutaneous leishmaniasis Antigens CD medicine Humans Th1-cytokines leishmaniasis Cell Proliferation Infection Control business.industry Perforin biomarkers Leishmaniasis Th1 Cells medicine.disease biology.organism_classification 030104 developmental biology inhibitory receptors biology.protein Leukocytes Mononuclear business CD8 |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Vol 8 (2018) |
| ISSN: | 2235-2988 |
| DOI: | 10.3389/fcimb.2018.00393 |
| Popis: | 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 TNAIVE 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 (TEM for CD4+ T cells and TEMRA for CD8+ T cells). The amount of antigen-specific CD57+/CD8+ TEMRA 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. |
| Databáze: | OpenAIRE |
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