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.
Akbar
A N
AN
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, United Kingdom.
Savill
J
J
Gombert
W
W
Bofill
M
M
Borthwick
N J
NJ
Whitelaw
F
F
Grundy
J
J
Janossy
G
G
Salmon
M
M
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