HLA-DR mediated cell death is associated with, but not induced by TNF-alpha 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 ac tivation. In antigen presenting cells (APC), TNF alpha increased antigen pr esentation, notably by up-regulation of HLA class II expression. In additio n to their rule in antigen presentation, HLA-DR molecules transduce intrace llular signals which lead to cytokine up-regulation or cell death. We have previously observed that the susceptibility of APC to HLA-DR mediated apopt osis increase throughout their maturation. We therefore investigated the re lationship between TNF alpha production and susceptibility to HLA-DR-mediat ed 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 susce ptibility and spontaneous TNF alpha release are correlated in these differe nt cells. However, while autocrine TNF alpha production was critical for DC maturation, upregulation of TNF alpha release after HLA-DR crosslinking ni as 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 parall el manner and that while TNF alpha may induce maturation of APC to an "apop tosis sensitive" stage, there is no direct role for TNF alpha in HLA-DR-med iated apoptosis of APC. (C) American Society for Histocompatibility and Imm unogenetics, 2001. Published by Elsevier Science Inc.