Critical role of CD4 T cells in PF4/heparin antibody production in mice. Blood 2015 Mar 12;125(11):1826-9
Date
01/18/2015Pubmed ID
25595736Pubmed Central ID
PMC4357587DOI
10.1182/blood-2014-09-603464Scopus ID
2-s2.0-84941938986 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
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.
Author List
Zheng Y, Yu M, Padmanabhan A, Aster RH, Yuan L, Wen R, Wang DAuthor
Richard H. Aster MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
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
