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 ؉ Leishmaniareactive 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-␥) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-␥ 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-␥, 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.

Cytokine profile in Montenegro skin test of patients with localized cutaneous and mucocutaneous leishmaniasis

“…In spite of that, the MST remains positive before and after treatment, and therefore, the MST response is independent from the treatment 8 , although we cannot be certain about the changes of the MST intensity after treatment, as this has not been measured by the authors. In comparison with in vitro studies, the treatment does not change the immunological response of the patients with LCL, as demonstrated by some authors 1,13,30 . DA-CRUZ et al 13 demonstrated in peripheral blood of patients with localized cutaneous leishmaniasis caused by L. braziliensis, that the type of cytokine remains the same, i.e., the Th1 type, before and after the treatment.…”

“…In comparison with in vitro studies, the treatment does not change the immunological response of the patients with LCL, as demonstrated by some authors 1,13,30 . DA-CRUZ et al 13 demonstrated in peripheral blood of patients with localized cutaneous leishmaniasis caused by L. braziliensis, that the type of cytokine remains the same, i.e., the Th1 type, before and after the treatment. This fact supports our findings in the MST that was performed after treatment in two patients of LCL.…”

“…This fact supports our findings in the MST that was performed after treatment in two patients of LCL. However, in MCL patients, a change in cytokine profile after treatment has been observed in vitro, as the observed Th1 and Th2 types, changed to Th1 type 11,13 .…”

“…The immune response of the New World LCL caused by L. braziliensis, is characterized by a Th1 response, with a predominance of IFN-gamma expression in vitro and in situ and a very low or sometimes absent expression of IL-4, IL-5 and IL-10 1,2,5, [11][12][13][14][15]20 . In relation to other cytokines, such as IL-2, they have been demonstrated in vitro and in situ, with a low expression.…”

“…Differently, in this context, cytokines may play different roles in the pathogenesis, being more related to the maintenance of the inflammatory reaction in the tissue. Studies in this context have identified both Th1 and Th2-type cytokines in Leishmania antigen-stimulated peripheral blood mononuclear cell supernatant in LCL 11,13,15 and also in MCL 13 . PCR studies of lesion samples have shown Th1 profile LCL and both Th1 and Th2 in MCL 26 .…”