Activation of human naïve CD8 T cells by artificial antigen presenting cells (132.31)

Abstract

Abstract The precise mechanisms by which an activated T cell differentiates to a memory cell remain unclear. Recent evidence indicates that asymmetric cell division (ACD), an evolutionarily conserved process whereby multiple cell fates are derived from a common progenitor cell, may play an important role in the differentiation of T cells. However, these studies were conducted in mouse models and it is unknown whether parallel mechanisms occur in human T cells. To better understand these mechanisms, we employed the use of an established artificial antigen presenting cell (aAPC) system for the activation of human naïve CD8 T cells. Our efforts have focused on the early events following T cell activation up to the first division of T cells. We investigated atypical protein kinase C zeta (PKCζ), a protein involved in ACD, and its role in human CD8 T cell differentiation upon engagement of the T cell receptor. Anti-CD3 presentation to T cells by the aAPCs resulted in the partitioning of PKCζ distal to the immunological synapse in a temporal manner. This polarization was first observed at 12 hours following activation and was maintained for at least up to 42 hours of stimulation. However, in the absence of anti-CD3 stimulation by the aAPC, polarization of PKCζ did not occur in the T cells. These data indicate that partitioning of polarization complex proteins occurs in human T cells and may be important in the differentiation of CD8 T cell subsets following activation.