Critical role of CD4 T cells in PF4/heparin antibody production in mice.

Abstract

Antibodies specific for platelet factor 4 (PF4)/heparin complexes are central to the pathogenesis of heparin-induced thrombocytopenia. Marginal zone B cells appear to be the source of such antibodies, but whether T-cell help is required is unclear. Here, we showed that induction of PF4/heparin-specific antibodies by PF4/heparin complexes was markedly impaired in mice depleted of CD4 T cells by anti-CD4 antibodies. Furthermore, Rag1-deficient recipient mice produced PF4/heparin-specific antibodies upon PF4/heparin challenge when reconstituted with a mixture of wild-type splenic B cells and splenocytes from B-cell-deficient (μMT) mice but not splenocytes from T- and B-cell-deficient (Rag1 knockout) mice. Lastly, mice with B cells lacking CD40, a B-cell costimulatory molecule that helps T-cell-dependent B-cell responses, displayed a marked reduction of PF4/heparin-specific antibody production following PF4/heparin challenge. Together, these findings show that helper T cells play a critical role in production of PF4/heparin-specific antibodies.

• Authors: Yongwei Zheng, Mei Yu, Anand Padmanabhan, Richard H Aster, Liudi Yuan, Renren Wen, Demin Wang
• Journal: Blood (Blood) Vol. 125 Issue 11 Pg. 1826-9 (Mar 12 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25595736 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• Homeodomain Proteins
• RAG-1 protein
• Platelet Factor 4
• Heparin

Topics

• Adoptive Transfer
• Animals
• Antibody Formation
• Antibody Specificity
• B-Lymphocytes (immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Disease Models, Animal
• Heparin (adverse effects, chemistry, immunology)
• Homeodomain Proteins (genetics, immunology)
• Humans
• Immunization
• Lymphocyte Depletion
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Platelet Factor 4 (chemistry, immunology)
• Thrombocytopenia (blood, etiology, immunology)
• Transplantation Chimera