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

• Published in: Frontiers in cellular and infection microbiology Vol. 8; p. 393
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.11.2018
• Subjects: biomarkers; CD8+ and CD4+ T-cells; Cellular and Infection Microbiology; Leishmania; leishmaniasis; paraflagellar rod protein-1; phenotype; phenotype; Th1-cytokines; paraflagellar rod protein-1; Leishmania; biomarkers; inhibitory receptors; CD8+ and CD4+ T-cells; leishmaniasis
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2018.00393

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 (S A) or (S A) or with a recombinant paraflagellar rod protein-1 (rPFR1). Higher frequencies of antigen-specific T 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 for CD4 T cells and T for CD8 T cells). The amount of antigen-specific CD57 /CD8 T 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 infection.