The CD40 ligand (CD40L) protein, which is involved in the regulation of both humoral and cellular immune responses, is expressed predominantly on the surface of activated CD4+ T cells. T cell activation via phorbol 12-myristate 13-acetate (PMA) + ionomycin or anti-CD3 mAb stimulation causes a rapid, but transient induction of CD40L mRNA and surface expression. To determine whether the regulation of CD40L mRNA stability might contribute to this induction under different conditions of T cell activation, CD4+ T cells were isolated from human peripheral blood and stimulated for various lengths of time with either PMA + ionomycin or plate-bound anti-CD3 mAb. After treatment of activated cells with the transcriptional inhibitor Actinomycin D, Northern analysis revealed that the stability of the CD40L message varies depending on the type and duration of T cell activation. PMA + ionomycin stimulation for 1 hr resulted in a stable CD40L message. In contrast, the CD40L message was very unstable after short periods of anti-CD3 stimulation, but the stability increased dramatically after 24 hrs of anti-CD3 activation. Subsequent analysis of the stability of TNF-alpha and c-myc mRNAs under identical conditions of T cell activation showed patterns of regulation that were different from CD40L. Taken together, these data suggest that T cell activation may regulate CD40L expression by post-transcriptional control of mRNA stability. Additionally, the mechanisms controlling CD40L message stability might be distinct from those involved in the post-transcriptional regulation of the TNF-alpha and c-myc genes.
|Original language||English (US)|
|State||Published - Mar 20 1998|
All Science Journal Classification (ASJC) codes
- Molecular Biology