Kinetics of the CTLA-4 isoforms expression after T-lymphocyte activation and role of the promoter polymorphisms on CTLA-4 gene transcription

Cytotoxic T lymphocyte antigen 4 (CTLA-4) plays a key inhibitory role during T lymphocyte activation. The CTLA4 gene is translated into two proteic isoforms: a full-length protein (flCTLA-4) and a soluble counterpart. We explored the expression of both isoforms on healthy subjects. Whereas in non-stimulated cells the flCTLA-4 isoform is predominant, after stimulation the expression of the soluble form rapidly increases, reaching its maximum 24 h after and falling again to the basal levels 72 h after stimulation. In contrast, the flCTLA-4 mRNA levels increase is slower, reaching the maximum level 72 h after stimulation. The presence of the T allele in the promoter positions −1722 and −318 is associated with an increased transcriptional activity and this effect seems to be synergic. We conclude that the kinetics of CTLA-4 isoform expression are sequential, and that the promoter polymorphisms −1722(C/T) and −318(C/T) are involved in the control of the CTLA4 transcription.