Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-29T22:53:27Z No. of bitstreams: 1 JoaoFirminoRodriguesNeto_TESE.pdf: 2194031 bytes, checksum: fb646e671a736d92f6d4e5cc3cc5acc2 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-02T00:38:57Z (GMT) No. of bitstreams: 1 JoaoFirminoRodriguesNeto_TESE.pdf: 2194031 bytes, checksum: fb646e671a736d92f6d4e5cc3cc5acc2 (MD5) / Made available in DSpace on 2016-03-02T00:38:57Z (GMT). No. of bitstreams: 1 JoaoFirminoRodriguesNeto_TESE.pdf: 2194031 bytes, checksum: fb646e671a736d92f6d4e5cc3cc5acc2 (MD5) Previous issue date: 2015-04-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / A leishmaniose visceral (LV) ? uma doen?a end?mica em muitos pa?ses, incluindo o Brasil. O protozo?rio Leishmania infantum ? o agente etiol?gico da LV, sendo transmitido pela picada das f?meas dos flebotom?neos, durante o repasto sangu?neo. A maioria dos indiv?duos quando expostos ao parasita n?o desenvolvem a doen?a, pois apresentam um predom?nio da resposta celular Th1. Aqueles que desenvolvem doen?a, apresentam sinais como febre, perda de peso, hepatoesplenomegalia e um comprometimento da resposta imune celular, espec?fica a ant?genos de Leishmania. N?s avaliamos se essa anergia, observada durante a doen?a ativa, poderia estar associada com altera??es nas mol?culas coestimulat?rias de linf?citos T ou em seus ligantes em mon?citos CD14+. H? aumento na porcentagem de CTLA-4 em linf?citos T CD4+ (p=0,001) e ICOS em linf?citos T CD4+ e CD8+ (p=0,002 para CD4+ e p=0,003 para CD8+) ap?s est?mulo por ant?geno sol?vel de Leishmania (SLA) na LV sintom?tica, e que h? maior porcentagem dessas mol?culas ex vivo, quando comparados indiv?duos sintom?ticos aos recuperados (p=0,04 para CTLA-4 em CD4+, e p=0,001 para ICOS em CD4+ e p=0,026 para CD8+). Al?m disso, encontramos uma maior express?o dos genes CTLA-4, OX-40 e ICOS, durante a LV ativa. As mol?culas CD40, CD80, CD86, HLA-DR e ICOSL, n?o sofrem altera??o durante a doen?a. H? produ??o de IFN-? por c?lulas de sangue perif?rico, ap?s est?mulo por SLA, em indiv?duos sintom?ticos; no entanto, h? diminui??o na raz?o entre IFN-?/IL-10, com aumento desta ap?s a cura. A observa??o do comprometimento de algumas vias de mol?culas coestimulat?rias poderia diminuir a capacidade microbicida dos fag?citos, durante a leishmaniose visceral sintom?tica, podendo facilitar a sobreviv?ncia e a prolifera??o do parasita. / Visceral leishmaniasis (VL) is endemic in many countries, including Brazil. The protozoan Leishmania infantum, is the etiological agent of VL, and is transmitted by the bite of female sandflies during the blood meal. The majority of subjects when exposed to the parasite do not develop the disease, because of development of Th1 cellular responses. Those who have develop signs of VL such as fever, weight loss, hepatosplenomegaly, have impairment of the cellular immune response, specific to the Leishmania antigens. We evaluated whether the specififc anergy during symptomatic VL, may be associated with changes in T cells costimulatory molecules or their ligands in CD14+ monocytes. There is an increase in CTLA-4 porcentage on CD4+ T lymphocytes (p=0.001) and ICOS on CD4+ and CD8+ T cells (p=0.002 to CD4+ and p=0.003 to CD8+), after stimulation by soluble Leishmania antigen (SLA) during active visceral leishmaniasis, and that there is a higher percentage of these molecules ex vivo, when comparing symptomatic to recovered individuals (p=0.04 to CTLA-4 in CD4+, and p=0.001 to ICOS in CD4+ and p=0.026 to CD8+). Moreover, we found a high gene expression of CTLA-4, OX-40 and ICOS during active VL. CD40, CD80, CD86, HLA-DR and ICOSL molecules do not suffer changes during disease. There is IFN-? production by the peripheral blood cells, after SLA stimulation, by peripheral blood cells in symptomatic subjects; however, there is a decrease of the ratio IFN-?/IL-10, which is reversed after clinical recovery. The impairment of some costimulatory molecules pathways during symptomatic VL could inhibit the ability of phagocytes to kill Leishmania and could facilitate their survival and the proliferation inside macrophages.