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Published on: July 28, 2010
Immunologic patterns associated with cure in human American cutaneous leishmaniasis
S G Coutinho1, A M Da-Cruz, A L Bertho
1Laboratório de Imunidade Celular e Humoral, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brasil. coutinho@gene.dbbm.fiocruz.br
Insights
Investigating American cutaneous leishmaniasis, this study found distinct T cell responses. Healed lesions show a beneficial pattern with CD4+ and CD8+ T cells producing gamma interferon (IFN-gamma).
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- American cutaneous leishmaniasis is a parasitic disease with variable clinical outcomes.
- Understanding the host immune response is crucial for developing effective treatments.
- T cell subsets and cytokine profiles play a significant role in leishmaniasis pathogenesis.
Purpose of the Study:
- To characterize T cell proliferative responses and cytokine production in patients with American cutaneous leishmaniasis.
- To compare immune responses during active disease versus healed lesions.
- To identify immune correlates associated with disease resolution.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from patients were stimulated in vitro with Leishmania braziliensis antigens.
- Lymphocyte proliferation assays were performed.
- CD4 and CD8 T cell phenotypes were analyzed.
- Cytokine levels (IFN-gamma and IL-4) in culture supernatants were measured using specific assays.
Main Results:
- During active disease, a predominance of CD4+ T cells responded, producing a mixed pattern of Type 1 (IFN-gamma) and Type 2 (IL-4) cytokines.
- In healed lesions, similar proportions of CD4+ and CD8+ T cells responded.
- Healed lesions were associated with Type 1 cytokine production (IFN-gamma) and minimal IL-4.
Conclusions:
- The T cell response shifts during the course of American cutaneous leishmaniasis.
- A Type 1 immune response involving both CD4+ and CD8+ T cells correlates with successful healing.
- This pattern suggests a beneficial role for cell-mediated immunity in resolving cutaneous leishmaniasis.
Abstract:
Patients with American cutaneous leishmaniasis were studied before therapy (active lesion) and at the end of therapy (cured patients). Assays of lymphocyte proliferative responses of peripheral blood mononuclear cells induced in vitro by Leishmania braziliensis promastigote antigens (Lb) were performed. Antigen-stimulated cells were harvested for CD4 and CD8 phenotype analysis and the levels of gamma interferon (IFN-gamma) and interleukin 4 (IL-4) produced were also determined in the culture supernatants. Two different patterns of Lb-induced T cell responses were observed: a) predominance of responding CD4+ cells and mixed type 1 and type 2 cytokine production (IFN-gamma and IL-4) during the active disease, and b) similar proportions of responding CD4+ and CD8+ cells, and type 1 cytokine production (presence of IFN-gamma and very low IL-4) at the end of therapy (healed lesions). This last pattern is probably associated with a beneficial T cell response.
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