HLA‐A and HLA‐B transcription decrease with ageing in peripheral blood leucocytes

Immunosenescence involves modifications of humoral and cellular immunity. In a previous study, we have shown a locus‐dependent reduction of HLA class‐I cell surface expression on peripheral lymphocytes and monocytes with advancing age. Here we report the quantitative analysis of HLA‐A and ‐B transcripts from PBL of 54 healthy subjects aged 21–90 years. Using a competitive RT‐PCR method, we observed a significant decrease of HLA‐A (P < 0·0001) and ‐B (P = 0·0025) mRNA contents with increasing age. Secondly, to investigate this locus‐dependent alteration of HLA class‐I transcription, we performed EMSA using nuclear extracts from PBL of five young (24–31‐year‐old) and 5 elderly (58–69 years old) donors with locus A and B sequences of the Enh‐A as probes. No qualitative variation of EMSA profiles appeared between the two groups of donors with 6 and 4 bandshift for the locus A and B, respectively. Quantitatively, we observed a significant increase of B4 intensity in the elderly group compared to the young group (P < 0·05). These results suggest that the variation of DNA binding protein could contribute to the lower transcription of HLA‐A and ‐B with ageing. These alterations of HLA class‐I expression at the transcriptional level could lead to the unresponsiveness of CD8 T cells due to default of antigen presentation with ageing.

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