Brief report PF4/heparin complexes are T cell–dependent antigens

is a life-threatening, thrombotic disorder associated with development of anti– platelet factor 4 (anti-PF4)/heparin autoan-tibodies. Little is known about the anti-genic and cellular requirements that initiate the immune response to these complexes. To begin to delineate mecha-nisms of autoantibody formation in HIT, we studied the immunizing effects of mu-rine PF4 (mPF4)/heparin in mice with and without thymic function. Euthymic mice were injected with mPF4/heparin complexes, mPF4, heparin, or buffer. Mice injected with mPF4/heparin, but not mPF4 or heparin alone, developed heparin-dependent au-toantibodies that shared serologic and functional characteristics of human HIT antibodies, including preferential binding to mPF4/heparin complexes and causing heparin- and FcRIIA-dependent platelet activation. In contrast, athymic mice did not develop HIT-like antibodies. Taken together, these studies establish that PF4/ heparin complexes are highly immuno-genic and elicit self-reacting anti-PF4/ heparin antibodies in a T cell–dependent manner. (Blood. 2005;106:929-931) © 2005 by The American Society of Hematolog