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

Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine involved in inflammatory responses which can trigger both cell apoptosis and cell activation. In antigen presenting cells (APC), TNF alpha increased antigen presentation, notably by up-regulation of HLA class II expression. In addition to their rule 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 TNF alpha production and susceptibility to HLA-DR-mediated apoptosis of different APC. The hematopoietic 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 and spontaneous TNF alpha release are correlated in these different cells. However, while autocrine TNF alpha production was critical for DC maturation, upregulation of TNF alpha release after HLA-DR crosslinking nias not observed and neutralization. of endogenous TNF alpha did not modify HLA-DR-mediated apoptosis. These data reveal that HLA-DR mediated apoptosis susceptibility and spontaneous TNF alpha release are regulated in a parallel manner and that while TNF alpha may induce maturation of APC to an "apoptosis sensitive" stage, there is no direct role for TNF alpha in HLA-DR-mediated apoptosis of APC. (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.