Cellular immune responses to Bacillus Calmette-Guerin vaccine from health and human immunodeficiency virus-exposed.

Orientadores: Maria Marluce dos Santos Vilela, Marcos Tadeu Nolasco da SilvaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Este estudo teve como objetivo analisar se há associação entre a viremia plasmática do Vírus da Imunodeficiência Humana (HIV) e a resposta imunológica adaptativa de crianças e adolescentes com infecção vertical pelo HIV-1 em uso de terapia antirretroviral combinada (TARVc). Os pacientes foram recrutados no Ambulatório de Imunodeficiência Secundária Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas e no Centro de Orientação e Apoio Sorológico (COAS), em Jundiaí, ambos no estado de São Paulo, Brasil. Constituíram-se dois grupos de pacientes: a) com controle virológico sustentado por mais de um ano (Carga viral - CV 1000 cópias/mL. Crianças e adolescentes saudáveis participaram como controles. Foram realizadas, por citometria de fluxo, imunofenotipagens de linfócitos T CD4+, T CD8+, B total e de memória e a proliferação de linfócitos T em culturas de células mononucleadas do sangue periférico estimuladas com HIV-1 inativado por aldritiol-2. A concentração de citocinas IL-2, IL-4, IL-5, IL-10, IFN-?, IFN-?, TNF-? e TGF-?1 no sobrenadante destas culturas foi analisada com Cytometric Bead Array e Enzyme-Linked Immunosorbent Assay. Também foram dosados imunoglobulinas por nefelometria; anticorpos anti-hepatite B e anti-rubéola por Chemiluminescent Microparticle Immunoassay e anti-tétano e anti-difteria por Toxin Binding Inhibiton test. Empregaram-se os testes estatísticos de Kruskal-Wallis, Wilcoxon, Mann-Whitney, exato de Fisher, Comparações Múltiplas Não Paramétricas e Correlação de Spearman, sendo o nível de significância de p 1,000 copies/mL. Healthy children and adolescents participated in the study as controls. Aldrithiol-2-inactivated HIV-1-stimulated peripheral blood mononuclear cells were cultured to evaluate HIV-specific lymphoproliferation by flow cytometry and IL-2, IL-4, IL-5, IL-10, IFN-?, IFN-?, TNF-? and TGF-?1 concentration by Cytometric Bead Array and Enzyme-Linked Immunosorbent Assay. Adaptative immunity was also evaluated with T CD4+, T CD8+, total and memory B cell counts by flow cytometry, immunoglobulin dosage by nephelometry, Chemiluminescent Microparticle Immunoassay to antibodies anti-hepatitis B and anti-rubella and Toxin Binding Inhibiton test to anti-tetanus and anti-diphtheria were carried out to humoral response evaluation. Kruskal-Wallis, Wilcoxon, Mann-Whitney, Fisher's exact, Nonparametric Multiple Comparisons and Spearman Correlation tests were used, with a p value < 0.05. There was no difference in T CD8, total and memory B cell counts between the groups of patients. T CD4 cell numbers were decreased in the viremic group at the time humoral immunity was performed. Greater memory B cell counts were observed among patients with UVL who were younger at cART beginning. IgM and IgG levels were higher in viremic patients in comparison to control and patients with UVL, which had increased levels of IgA in comparison to controls. There was no difference in the proportion of responders for tetanus, diphtheria, rubella and hepatitis B vaccines between the two groups of patients; nevertheless, the group with UVL showed higher titers of anti-hepatitis B, anti-rubella and anti-tetanus than the viremic group. Controls showed higher frequency of responders to diphtheria, rubella and hepatitis B and titers to anti-hepatitis B, anti-rubella and anti-tetanus in comparison to patients. Patients with UVL showed higher HIV-1-specific T lymphocyte proliferation and IL-2 and IFN-? production in comparison to viremic patients. Greater time since the start of successful cART in patients with UVL was associated with higher proliferation and IFN-? and IL-2 levels in cultures with HIV. Among viremic patients, HIV-specific proliferation was lower in individuals who started ART after one year of age, and IFN-? concentration was inversely correlated with VL. We concluded that sustained HIV-1 virologic control was valuable on mounting responses to HIV and vaccines and the early initiation of ART contributed to improved HIV cellular immunity and greater memory B cell countsDoutoradoSaude da Criança e do AdolescenteDoutora em Ciência