A variable immunoreceptor in a subpopulation of human neutrophils.
Neutrophils are thought to rely solely on nonspecific immune mechanisms. Here we provide molecular biological, immunological, ultrastructural, and functional evidence for the presence of a T cell receptor (TCR)-based variable immunoreceptor in a 5-8% subpopulation of human neutrophils. We demonstrate that these peripheral blood neutrophils express variable and individual-specific TCRalphabeta repertoires and the RAG1/RAG2 recombinase complex. The proinflammatory cytokine granulocyte colony-stimulating factor regulates expression of the neutrophil immunoreceptor and RAG1/RAG2 in vivo. Specific engagement of the neutrophil TCR complex protects from apoptosis and stimulates secretion of the neutrophil-activating chemokine IL-8. Our results, which also demonstrate the presence of the TCR in murine neutrophils, suggest the coexistence of a variable and an innate host defense system in mammalian neutrophils.
Puellmann
Kerstin
K
Institute for Clinical Chemistry, University of Heidelberg, 68167 Mannheim, Germany. kerstin.puellman@web.de
Kaminski
Wolfgang E
WE
Vogel
Mandy
M
Nebe
C Thomas
CT
Schroeder
Josef
J
Wolf
Hans
H
Beham
Alexander W
AW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000378:metabolism; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins; D045522:Recombinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism
D017252:CD3 Complex; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D016209:Interleukin-8; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D045522:Recombinases; D051020:bcl-X Protein; C064658:RAG-1 protein; D016179:Granulocyte Colony-Stimulating Factor