HLA-DR mediated cell death is associated with, but not induced by TNF-α secretion in APC

Abstract

Tumor necrosis factor α (TNFα) is a pleiotropic cytokine involved in inflammatory responses which can trigger both cell apoptosis and cell activation. In antigen presenting cells (APC), TNFα increased antigen presentation, notably by up-regulation of HLA class II expression. In addition to their role in antigen presentation, HLA-DR molecules transduce intracellular signals which lead to cytokine up-regulation or cell death. We have previously observed that the susceptibility of APC to HLA-DR mediated apoptosis increase throughout their maturation. We therefore investigated the relationship between TNFα production and susceptibility to HLA-DR-mediated apoptosis of different APC. The hematopoieric progenitor cell line (KG1), monocytic cell line (THP-1), monocyte-derived dendritic cell (DC), and B-lymphoid cell line (Raji) have been studied. We report that apoptosis susceptibility lease are correlated in these different cells. However, while autocrine TNFα production was critical for DC maturation, upregulation of TNFα release after HLA-DR crosslinking was not observed and neutralization of endogenous TNFα did not modify HLA-DR-mediated apoptosis. These data reveal that HLA-DR mediated apoptosis susceptibility and spontaneous TNFα release are regulated in a parallel manner and that while TNFα may induce maturation of APC to an "apoptosis sensitive" stage, there is no direct role for TNFα in HLA-DR-mediated apoptosis of APC. © American Society for Histocompatibility and Immunogenetics, 2001.