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Critical role of CD4 T cells in PF4/heparin antibody production in mice. Blood 2015 Mar 12;125(11):1826-9

Date

01/18/2015

Pubmed ID

25595736

Pubmed Central ID

PMC4357587

DOI

10.1182/blood-2014-09-603464

Scopus ID

2-s2.0-84941938986   12 Citations

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 (╬╝MT) 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.

Author List

Zheng Y, Yu M, Padmanabhan A, Aster RH, Yuan L, Wen R, Wang D

Authors

Richard H. Aster MD Professor in the Medicine department at Medical College of Wisconsin
Anand Padmanabhan MD, PhD Associate Professor in the Pathology department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adoptive Transfer
Animals
Antibody Formation
Antibody Specificity
B-Lymphocytes
CD4-Positive T-Lymphocytes
Disease Models, Animal
Heparin
Homeodomain Proteins
Humans
Immunization
Lymphocyte Depletion
Mice
Mice, Inbred C57BL
Mice, Knockout
Platelet Factor 4
Thrombocytopenia
Transplantation Chimera
jenkins-FCD Prod-387 b0ced2662056320369de4e5cd5f21c218c03feb3