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.
Le Morvan
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Laboratoire d'Immunologie et Immunogénétique CNRS UMR 6101, Limoges, France.
Cogné
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Drouet
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D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D002457:Cell Extracts / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D015234:HLA-A Antigens / Q000096:biosynthesis* / Q000235:genetics; D015235:HLA-B Antigens / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D012333:RNA, Messenger