Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates

多型性のないT細胞レセプターとCD1d分子のシグナル遮断は血液型A型抗原に対する抗体産生を特異的に抑制する

Tazawa Hirofumi

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 demonstrated 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, those were not observed at all in CD1d-/- mice, which lack NKT cells. Administration of anti-mouse CD1d blocking mAb prior to the 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 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 the 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 ABOincompatible transplants.

Medical sciences [ 490 ]

eng

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[Created] 2014-11-21

Hirofumi Tazawa, Toshimitsu Irei, Yuka Tanaka, Yuka Igarashi, Hirotaka Tashiro and Hideki Ohdan; Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates; Blood 2013, 122(15):2582-2590 (doi: 10.1182/blood-2012-02-407452) references

[DOI] http://dx.doi.org/10.1182/blood-2012-02-407452 references

広島大学