| First Author | Zheng Y | Year | 2015 |
| Journal | Blood | Volume | 125 |
| Issue | 11 | Pages | 1826-9 |
| PubMed ID | 25595736 | Mgi Jnum | J:221915 |
| Mgi Id | MGI:5641828 | Doi | 10.1182/blood-2014-09-603464 |
| Citation | Zheng Y, et al. (2015) Critical role of CD4 T cells in PF4/heparin antibody production in mice. Blood 125(11):1826-9 |
| abstractText | 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 (muMT) 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. |
