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


Dr M. Drouet, Service d'Immunologie et Immunogénétique, CHRU Dupuytren, 2 avenue Martin Luther-King, 87042 Limoges cedex, France.  E-mail: drouet@unilim.fr


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.