In nonactivated PBMCs, CCR5 expression remained low and was unaffected by progesterone treatment. Addition of IL-2 following anti-CD3 activation of T cells resulted in marked up-regulation of CCR5 mRNA and protein expression, consistent with previous reports. , (53) Progesterone exerted a dose-dependent inhibitory effect on CCR5 protein expression in these activated cultures. This inhibitory effect of the hormone could be seen only when progesterone was added before cell activation and was present for the entire culture period; CCR5 expression was unaltered when progesterone was added after activation of the cells, including the time of peak CCR5 expression.
In view of the extensive discussion of the genetic determinants of the CCR5 receptor's expression, endocrinological variables affecting the expression of CCR5 should likewise merit much consideration. These should include CCR5 and CXCR4 downregulation by progesterone as well as cortisol's upregulation of CXCR4 receptors, and the implications of such endocrinological factors in the treatment of immune deficiency.