Decreased frequency and proliferative response of invariant Vα24Vβ11 natural killer T (iNKT) cells in healthy elderly

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Abstract
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 Vα24-JαQ genes, paired preferentially with a Vβ11 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 Vα24+Vβ11+ 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 Vα24+Vβ11+ iNKT cells in elderly donors. No significant differences were found in the expression of CD27, CD28, CD45RO, CD45RAbright, CD161, CD94 and NKG2D on iNKT cells from young and elderly individuals. Proliferation of Vα24+Vβ11+ iNKT cells in response to α-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 Vα24+Vβ11+ 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.