Subpopulações de linfócitos T associados a perda óssea em pessoas vivendo com HIV/AIDS com carga viral controlada

Abstract

With the advent of combined antiretroviral therapy (cART), the number of people living with HIV/AIDS (PLWHA) aged of 50 years and older is increasing and, with it, an incidence of age-dependent comorbidities, including bone loss. The cause of early bone loss in PLWHA is influenced by chronic immune activation and systemic inflammation. Such manifestations have been characterized by cell subsets of hyperactivated T lymphocytes and factors secreted by them and, therefore, an evaluation of these subsets can serve as inflammatory markers in bone disease associated with HIV. The aim of the study is to evaluate CD4+ and CD8+ T cell subsets associated with bone loss in PLWHA with undetectable viral loads. The study was carried out at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado where the recruitment was carried out by convenience with 50 patients over 40 years of age that were submitted to dual energy X-ray absorptiometry (DXA) for bone densitometry examination. Blood samples were collected for isolation of peripheral blood mononuclear cells that were cryopreserved at -80º C until use. The phenotyping of TCD4+ and TCD8+ cell subsets were performed by flow cytometry for cells with regulatory profile (PD-1 and CTLA-4), activation (HLA-DR), proliferative activity (Ki-67) and IL-10-, IFNγ- and TNFα producing cells. Of the 50 patients, 48 returned with DXA exams: 13 osteoporosis (4 Men and 9Women), 23 osteopenia (14M, 9W) and 13 normal (10M, 2W). For immunophenotyping, samples of 34 PLWHA had cell viability above 90% after thawing and grouped into: normal (11M) and osteopenia (10M; 9W). Four samples from women with osteoporosis were not included due no counterpart of male samples. Data show that the CD4+ and CD8+ T cell subsets of osteopenic PLWHA have greater proliferative activity and higher levels of HLADR and CD69 than subsets of those with no bone loss. Regarding the regulatory profile, osteopenic PLWHA have a smaller number of CD4+CD3+CTLA-4+ and CD8+CD3+PD-1+ cells than with those with no bone loss. In addition, the intracytoplasmic expression of IFNγ and TNFα by CD4+CD3+CTLA-4+ cells showed unequal behavior between PLWHA with or without bone loss. The same divergence occurred with intracytoplasmic IFNγ levels in CD8+ PD1+ T cells. Our results suggest that these circulating CD4+ and CD8+ T cell subsets may have a role in the pathogenesis of osteopenia and osteoporosis in PLWHA.