RESUMO
To control immune responses, regulatory CD4+CD25+Foxp3+ T cells (Treg) maintain their wide and diverse repertoire through continuous arrival of recent thymic emigrants (RTE). However, during puberty, the activity of RTE starts to decline as a natural process of thymic involution, introducing consequences, not completely described, to the repertoire. Type 1 diabetes (T1D) patients show quantitative and qualitative impairments on the Treg cells. Our aim was to evaluate peripheral Treg and RTE cell frequencies, in T1D patients from two distinct age groups (young and adults) and verify if HLA phenotypes are concomitant associated. To this, blood samples from Brazilian twenty established T1D patients (12 young and 8 adults) and twenty-one healthy controls (11 young and 10 adults) were analyzed, by flow cytometry, to verify the percentages of CD4, Treg (CD4+CD25+Foxp3+) and the subsets of CD45RA+ (naive) and CD31+(RTE) within then. Furthermore, the HLA typing was also set. We observed that the young established T1D patients feature decreased frequencies in total Treg cells and naive RTE within Treg cells. Significant prevalence of HLA alleles, associated with risk, in T1D patients, was also identified. Performing a multivariate analysis, we confirmed that the cellular changes described offers significant variables that distinct T1D patients from the controls. Our data collectively highlight relevant aspects about homeostasis imbalances in the Treg cells of T1D patients, especially in young, and disease prognosis; that might contribute for future therapeutic strategies involving Treg cells manipulation.
Assuntos
Diabetes Mellitus Tipo 1 , Fatores de Transcrição Forkhead , Subunidade alfa de Receptor de Interleucina-2 , Linfócitos T Reguladores , Timo , Humanos , Diabetes Mellitus Tipo 1/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Brasil , Masculino , Feminino , Fatores de Transcrição Forkhead/metabolismo , Timo/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Adulto Jovem , Adolescente , Imunofenotipagem , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , CriançaRESUMO
To evaluate the levels of recent thymic emigrant (RTE) CD4+ T cells in HIV-infected children and to explore the associations among their frequency, antiretroviral treatment (ART) adherence, and CD4+ T cell restoration. The group evaluated comprised 85 HIV-infected patients classified as subjects with moderate or severe immunosuppression or as those with no evidence of immunosuppression. To evaluate the association between the frequency of RTE CD4+ T cells and ART adherence, 23 of the 85 patients were evaluated at two different time points during a one-year follow-up period. Children with severe immunosuppression had lower frequencies of RTE CD4+ T cells compared with children without evidence of immunosuppression (P < .001). The frequency of RTE CD4+ T cells in children with a high rate of adherence was significantly higher (P < .05) than that observed among those with suboptimal adherence. The latter group presented with infectious intercurrences on admission that decreased after initiation of treatment along with improved CD4+ and RTE naïve CD4+ T cells counts. The adequate ART adherence is essential for immune reconstitution, which might be reflected by the levels of RTE CD4+ T cells.