T-cell-mediated immune responses in patients with cutaneous or mucosal leishmaniasis: long-term evaluation after therapy

Abstract

T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4(+) and CD8(+) Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4(+) than CD8(+) T cells. In CL, the healing process was associated with a decrease of CD4(+) and an increase of CD8(+), leading to similar CD4(+) and CD8(+) proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4(+)/CD8(+) ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-gamma) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-gamma and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-gamma, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4(+) Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations.

FIG. 1.

Percentages of Leishmania-reactive CD4⁺ and CD8⁺ proliferating T cells in patients with CL (top panel) or ML (bottom panel) during the active disease, at end-T, at 6m-T, and 1 to 17 years after the end of therapy (long-term). Results are expressed as means ± standard errors of the means. Averages of the CD4⁺/CD8⁺ ratio are also represented.

FIG. 2.

IFN-γ production in supernatants of PBMCs stimulated in vitro with leishmanial antigens. Patients with CL or ML were evaluated during the active disease, at end-T, and 1 to 17 years after the end of therapy (long-term). Patients are represented by points, and means are indicated by lines.

FIG. 3.

IL-5 production in supernatants of PBMCs stimulated in vitro with leishmanial antigens. Patients with CL or ML were evaluated during the active disease, at end-T, and 1 to 17 years after the end of therapy (long-term). Patients are represented by points, and means are indicated by lines.