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Human CD4+ effector memory T cells are pre‐sensitized to Fas‐induced apoptosis due to more efficient receptor signaling
Author(s) -
Cruz Anthony C,
Ramaswamy Madhu,
Siegel Richard M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.846.12
Subject(s) - apoptosis , fas ligand , fadd , fas receptor , microbiology and biotechnology , lipid raft , biology , chemistry , programmed cell death , signal transduction , caspase , biochemistry
Naïve T cells activated through acute antigen stimulation expand and contract independently of the presence of the death receptor Fas. However, Fas‐FasL interactions play a critical role in TCR‐induced apoptosis of activated CD4 + T cells. Fas deficiency prompts the accumulation of CD44 + memory phenotype T cells in mice, suggesting Fas may play a more prominent role in apoptosis of memory T cells. The sensitivity of cells derived from naïve versus memory CD4 + T cells to Fas‐induced apoptosis has not been addressed. We compared the susceptibility of purified naïve versus memory human CD4 + T cells, both directly ex vivo and after in vitro activation and expansion, to undergo Fas‐induced apoptosis. Remarkably, effector memory phenotype (CD27 − CCR7 − ) cells were the most sensitive to non‐crosslinked anti‐Fas induced cell death. We have previously shown a correlation between lipid raft‐associated Fas and susceptibility to undergo apoptosis. Memory cells have increased lipid raft‐associated Fas surface protein versus naïve cells, which could account for increased sensitivity to Fas. Memory cells have more efficient assembly and activation of proximal Fas signaling components, including FADD and Caspase 8. These results suggest that effector memory cells have more efficient proximal Fas signaling and are intrinsically more sensitive to Fas‐induced apoptosis, possibly due to lipid raft localiztion of Fas.