Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates.
Previously, we detected B cells expressing receptors for blood group A carbohydrates in the CD11b(+)CD5(+) B-1a subpopulation in mice, similar to that in blood group O or B in humans. In the present study, we demonstrate that CD1d-restricted natural killer T (NKT) cells are required to produce anti-A antibodies (Abs), probably through collaboration with B-1a cells. After immunization of wild-type (WT) mice with human blood group A red blood cells (A-RBCs), interleukin (IL)-5 exclusively and transiently increased and the anti-A Abs were elevated in sera. However, these reactions were not observed in CD1d(-/-) mice, which lack NKT cells. Administration of anti-mouse CD1d blocking monoclonal Abs (mAb) prior to immunization abolished IL-5 production by NKT cells and anti-A Ab production in WT mice. Administration of anti-IL-5 neutralizing mAb also diminished anti-A Ab production in WT mice, suggesting that IL-5 secreted from NKT cells critically regulates anti-A Ab production by B-1a cells. In nonobese diabetic/severe combined immunodeficient (NOD/SCID/γc(null)) mice, into which peripheral blood mononuclear cells from type O human volunteers were engrafted, administration of anti-human CD1d mAb prior to A-RBC immunization completely inhibited anti-A Ab production. Thus, anti-CD1d treatment might constitute a novel approach that could help in evading Ab-mediated rejection in ABO-incompatible transplant recipients.
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Japan.
Hirofumi
H
Tazawa
Toshimitsu
T
Irei
Yuka
Y
Tanaka
Yuka
Y
Igarashi
Hirotaka
H
Tashiro
Hideki
H
Ohdan
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D055610:Antigens, CD1d / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002241:Carbohydrates / Q000276:immunology; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000017:ABO Blood-Group System; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D055610:Antigens, CD1d; D001323:Autoantibodies; C526877:CD1D protein, human; C584692:CD1d antigen, mouse; D002241:Carbohydrates; D015848:Interleukin-5