Exacerbated graft-versus-host disease in Pirb-/- mice.
Immune responses are often regulated by opposing receptor pairs that recognize the same ligand but deliver either activating or inhibitory signals. Paired immunoglobulin-like receptors (PIRs) expressed on B cells and myeloid cells comprise a major histocompatibility complex class I recognition system that regulates the responsiveness of these cells. Here, activating PIR-A and inhibitory PIR-B bound various mouse major histocompatibility complex class I (H-2) molecules, and in vitro H-2 tetramer stimulation of PIR-B on B cells or PIR-A on macrophages induced intracellular phosphotyrosine signaling. After transfer of allogeneic splenocytes into PIR-B-deficient mice, the mice showed exacerbated graft-versus-host disease, which was due to augmented activation of recipient dendritic cells with concomitant upregulation of PIR-A and increased interferon-gamma production. PIR-A-induced dendritic cell activation also led to increased proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions.
Nakamura
Akira
A
Department of Experimental Immunology and Core Research for Evolutional Science and Technology Program, Japan Science and Technology Agency, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan.
Kobayashi
Eiji
E
Takai
Toshiyuki
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D003713:Dendritic Cells / Q000378:metabolism; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D006183:H-2 Antigens; C105948:Pira1 protein, mouse; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic