title: 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.
authors.affiliation: Laboratory of Cellular and Humoral Immunology, Department of Immunology/Protozoology, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Alda Maria
authors.initials: AM
authors.lastname: Da-Cruz
authors.forename: Rita
authors.initials: R
authors.lastname: Bittar
authors.forename: Marise
authors.initials: M
authors.lastname: Mattos
authors.forename: Manuel P
authors.initials: MP
authors.lastname: Oliveira-Neto
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nogueira
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pinho-Ribeiro
authors.forename: Rilza Beatriz
authors.initials: RB
authors.lastname: Azeredo-Coutinho
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Coutinho
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000953:Antigens, Protozoan / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007892:Leishmania braziliensis / Q000276:immunology*; D007897:Leishmaniasis, Mucocutaneous / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged
chemical_list: D000953:Antigens, Protozoan; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma