CD52 ligation induces CD4 and CD8 down modulation in vivo and in vitro

Abstract

To successfully induce donor-specific tolerance after immune depletion, it is essential to understand the residual and recovering immune system in the context of the depleting agent because the properties of such a recovering immune system differ based on the depleting agent used. In this study, we investigate the phenotypic and functional characteristics of T cells exposed to Campath-1H in vivo and in vitro. Recovering T cells demonstrated down modulated surface CD4 and CD8 (by flow cytometry) for up to 45 days after Campath-1H administration. Additionally, these T cells had an activated phenotype. To determine whether this CD4/8 down modulation was due to T-cell activation only or in part due to Campath-1H, whole blood from healthy volunteers was exposed to Campath-1H and the surviving lymphocytes isolated. Flow cytometry revealed a dose-dependent down modulation of CD4/8 without T-cell activation. Additionally, these Campath-1H-treated T cells were immunocompetent as indicated by increased surface CD69 and interleukin-2 (IL-2) production following stimulation by soluble anti-CD3 mAb. In conclusion, Campath-1H by itself down modulates surface CD4 and CD8 without activating T cells.