Abstract

BackgroundLeishmaniasis is an important parasitic disease affecting millions worldwide. Human cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro, Brazil, where is caused by Leishmania braziliensis. The adaptive immune response is accountable for the healing of CL and despite of key role of CD8+ T cells in this immune response little is known about the CD8+ T lymphocytes frequencies, apoptosis and antigen-responsive CD8+ T lymphocytes of CL patients during antimonial therapy.MethodsUsing flow cytometry, we examined total and effector CD8+ T cells from CL patients before (PBT), during (PDT) and after (PAT) treatment for apoptosis and frequencies upon isolation and after in vitro L. braziliensis antigens (LbAg)-stimulation culture. Besides, a correlation study between immunological findings and lesion size was done.ResultsPDT showed lower frequencies of total CD8+ T lymphocytes and higher levels of apoptosis of these cells, which were also observed following LbAg-stimulation culture. Regarding effector CD8+ T cells, high frequencies were observed in PDT, while lower frequencies were observed in PAT. Interestingly, PDT showed higher frequencies of apoptotic-effector CD8+ T lymphocytes. Similar results were seen after in vitro antigenic-stimulation assays. Correlation analysis showed that the greater the size of lesion, the smaller the frequency of effector CD8+ T lymphocytes in PDT and PAT, as well as a positive correlation between apoptotic-effector CD8+ T cells frequency and lesion size of PDT.ConclusionsChanges in effector CD8+ T–lymphocyte frequencies, during and after treatment, seem to represent a critical stage to generate an efficient immune response and suggest that these cells would be evolved in the triggering or in the resolution of lesion, under the influence of therapy. This hypothesis opens new perspectives to clarify controversial statements about the protective or deleterious role of CD8+ T cells in the cure or aggravation of CL and the new approach of evaluating patients during treatment proved to be of utmost importance for understanding the immune response in the healing process of human CL.

Highlights

  • IntroductionHuman cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro, Brazil, where is caused by Leishmania braziliensis

  • Leishmaniasis is an important parasitic disease affecting millions worldwide

  • It is important to note that patients before treatment (PBT) and patients during treatment (PDT) showed lower percentages of CD8+CD45RA+CD27+ naïve T-cell subset when compared to healthy subjects (HS) and to patients after treatment (PAT), which could be a consequence of differentiation of naïve in effector CD8+ T cells, during active disease

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Summary

Introduction

Human cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro, Brazil, where is caused by Leishmania braziliensis. In Brazil, American tegumentary leishmaniasis (ATL) was registered in all states and is endemic in Rio de Janeiro, where it is caused mainly by Leishmania (Viannia) braziliensis, leading to a spectrum of clinical, immunological and histopathological manifestations, ranging from self-healing localized cutaneous leishmaniasis (CL) to destructive mucosal leishmaniasis [1,2]. Previous researches have focused mostly on immune responses during active phase and at the clinical cure of disease, the investigation of immunological patterns of patients during the antimonial therapy is critical for better understanding the establishment of pathology and for determine beneficial parameters of the immune responses associated with clinical cure

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