The specific recognition by macrophages of CD8+,CD45RO+ T cells undergoing apoptosis: a mechanism for T cell clearance during resolution of viral infections.
During viral infections, CD8+,CD45RO+ T populations expand. These primed cells express abundant levels of cytoplasmic granules that contain perforin and TIA-1. Recent work has suggested that the majority of this CD8+ population downregulates Bcl-2 protein expression and is destined to undergo apoptosis. In this study we have investigated the elimination of these apoptotic CD8+ T cells by both human monocyte-derived and murine bone marrow macrophages. We have found that these phagocytes recognize and ingest both apoptotic CD8+ and CD4+ T cells using an alpha v beta 3 (vitronectin receptor)/CD36/thrombospondin recognition system, with the same receptors being used in the recognition of apoptotic neutrophils. These data provide new evidence for a mechanism that enables the clearance of greatly increased populations of CD8+ effector cells which are found during viral infections. This enables cellular homeostasis to occur in the host upon resolution of viral diseases in vivo.
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, United Kingdom.
A N
AN
Akbar
J
J
Savill
W
W
Gombert
M
M
Bofill
N J
NJ
Borthwick
F
F
Whitelaw
J
J
Grundy
G
G
Janossy
M
M
Salmon
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D054353:Perforin; D010587:Phagocytosis; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis; D000074019:T-Cell Intracellular Antigen-1; D014777:Virus Diseases / Q000276:immunology*
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C499367:Tia1 protein, mouse; D054353:Perforin; D017493:Leukocyte Common Antigens