RESUMO
Invariant natural killer T (iNKT) cells represent a well-established T cell lineage characterised in humans by TCR consisting of an invariant alpha chain encoded by Valpha24-JalphaQ genes, paired preferentially with a Vbeta11 chain. iNKT cells also share some characteristics with NK cells, such as the expression of the NK-associated receptor CD161 in humans. The T cell immune response is the most dramatically affected by ageing, although age-associated alterations in the phenotype and function of other cells of the immune system have been demonstrated. Despite the importance of iNKT cells in the regulation of the immune response, there are a limited number of studies on the effect of ageing on peripheral blood iNKT cells. Thus, in this work we analyse the effect of ageing on peripheral blood Valpha24(+)Vbeta11(+) iNKT cells by studying their frequency, phenotype and proliferative function in elderly individuals fulfilling the SENIEUR criteria of healthy ageing compared with healthy young donors. Our results demonstrated a significant decrease of the percentage of Valpha24(+)Vbeta11(+) iNKT cells in elderly donors. No significant differences were found in the expression of CD27, CD28, CD45RO, CD45RA(bright), CD161, CD94 and NKG2D on iNKT cells from young and elderly individuals. Proliferation of Valpha24(+)Vbeta11(+) iNKT cells in response to alpha-GalCer and IL2 was analysed by calculating the cumulative population doubling (PD) after 14 days of culture. The PD levels were lower in the elderly indicating that Valpha24(+)Vbeta11(+) iNKT cells from healthy elderly subjects had an impaired proliferative capacity. These results indicate that ageing associates with a significant decline in the percentage and proliferative response of peripheral blood iNKT cells. Given the important immunoregulatory role of iNKT cells, these alterations in their number and function could contribute to the deleterious immune response in the elderly.
Assuntos
Envelhecimento/imunologia , Células Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Subpopulações de Linfócitos T/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Linhagem da Célula/imunologia , Proliferação de Células , Células Cultivadas , Senescência Celular/imunologia , Galactosilceramidas/metabolismo , Humanos , Interleucina-2/metabolismo , Células Matadoras Naturais/metabolismo , Contagem de Linfócitos , Fenótipo , Valores de Referência , Subpopulações de Linfócitos T/metabolismoRESUMO
This study was designed to investigate the effect of melatonin on the fatty acid composition of plasma and tissue lipids. Melatonin administration to rats fed with a standard diet only increased long-chain n-6 polyunsaturated fatty acids (PUFA) in total plasma lipids and liver phospholipids but induced significant changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses changes were reversed by melatonin administration. The analysis of lipid fractions revealed that only the cholesteryl ester fraction was affected by melatonin. Histological studies of the carotid artery intima revealed the appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of foam cells covered by the endothelium and by a thin layer of mononucleated cells. These changes were prevented by melatonin. We conclude that long-term melatonin administration modifies the fatty acid composition of rat plasma and liver lipids and ameliorates the arterial fatty infiltration induced by cholesterol.
