title: Multifunctional CD4⁺ T cells in patients with American cutaneous leishmaniasis.
abstract: Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis.
authors.affiliation: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: A B B
authors.initials: AB
authors.lastname: Macedo
authors.forename: J C
authors.initials: JC
authors.lastname: Sánchez-Arcila
authors.forename: A O
authors.initials: AO
authors.lastname: Schubach
authors.forename: S C F
authors.initials: SC
authors.lastname: Mendonça
authors.forename: A
authors.initials: A
authors.lastname: Marins-Dos-Santos
authors.forename: M
authors.initials: M
authors.lastname: de Fatima Madeira
authors.forename: T
authors.initials: T
authors.lastname: Gagini
authors.forename: M I F
authors.initials: MI
authors.lastname: Pimentel
authors.forename: P M
authors.initials: PM
authors.lastname: De Luca
mesh_terms: D000328:Adult; D000953:Antigens, Protozoan / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007892:Leishmania braziliensis / Q000276:immunology; D007894:Leishmania mexicana / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; C508594:IL2 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma