title: Leishmania braziliensis-reactive T cells are down-regulated in long-term cured cutaneous Leishmaniasis, but the renewal capacity of T effector memory compartments is preserved.
abstract: Leishmania (Viannia) braziliensis control and tissue damage relate to the effector immune response, which in turn affects clinical outcome. Leishmania reactive CD4(+) and CD8(+) T cells are expanded in long-term healed cutaneous leishmaniasis (hCL) patients but their functional characteristics remain to be determined. This study investigates antigen-specific recall in long-term healed CL caused by L. braziliensis infection. Healed CL subjects were grouped according to the time elapsed since the end of therapy: less than two years and two to five years. Activation phenotype (CD69(+) or CD25(+)) and subpopulations of memory T cell phenotypes [central memory (Tcm): CD45RO(+) CCR7(+) or effector memory (Tem): CD45RO(+) CCR7(-)] were quantified in ex vivo blood mononuclear cells and after Leishmania antigens stimuli. A reduction in the percentage of activated Leishmania-responder CD4(+) and CD8(+) T cells in hCL was associated with the time elapsed since clinical cure. Percentage of CD69(+) in TCD4(+) and TCD8(+) cells were negatively correlated with IL-10 levels. Ex vivo analyses showed contracted Tem CD4(+) and Tem CD8(+) compartments from hCL with long time elapsed since clinical cure, although renewal of these compartments was observed following in vitro exposure to leishmanial stimuli. Our results show that healed L. braziliensis infected patients exhibit a recall response to Leishmania antigens with evident expansion of effector memory T cells. Regulated leishmanial-specific response seems to emerge only about two years after initial contact with the parasite antigens.
authors.affiliation: Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Regina
authors.initials: R
authors.lastname: Pereira-Carvalho
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Mendes-Aguiar
authors.forename: Manoel P
authors.initials: MP
authors.lastname: Oliveira-Neto
authors.forename: Cláudia J F
authors.initials: CJ
authors.lastname: Covas
authors.forename: Alvaro L
authors.initials: AL
authors.lastname: Bertho
authors.forename: Alda M
authors.initials: AM
authors.lastname: Da-Cruz
authors.forename: Adriano
authors.initials: A
authors.lastname: Gomes-Silva
mesh_terms: D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines