INDIRECT ALLORECOGNITION OF PLATELETS BY T-HELPER CELLS DURING PLATELET TRANSFUSIONS CORRELATES WITH ANTI-MAJOR HISTOCOMPATIBILITY COMPLEX ANTIBODY AND CYTOTOXIC T-LYMPHOCYTE FORMATION

To study the cellular immunology of platelet-induced alloimmunization, a murine transfusion model was developed, BALB/c (H-2(d)) recipient mice were transfused weekly with 2 x 10(8) platelets or 10(3) leukocytes from C57BL/6 (H-2(b)) donor mice, Recipient antidonor major histocompatibility complex (MHC) class I alloantibodies could be detected in flow cytometric assays by the fifth platelet transfusion, In contrast, when leukocytes only were transfused, alloantibodies were not detected. In vitro assays demonstrated that murine H-2(b) platelets were positive for MHC class 1 expression but lacked MHC class II molecules on their membranes and were unable to stimulate proliferation or cytokine production when incubated with naive H-2(d) spleen cells. In vivo, however, platelet transfusions induced two distinct patterns of cell-mediated reactivity. First, during the initial transfusions and before alloantibody formation, there was induction of T-cell anergy, characterized by the inability of recipient T cells to respond to Concanavalin A (ConA) or to proliferate in an antidonor mixed lymphocyte reaction (MLR), together with suppressed natural killer (NK) cell activity. This unresponsiveness was associated with a transient increase in nitric oxide (NO)-dependent cytotoxicity and interleukin-1 (IL-1) production. Second, once alloantibodies developed, significantly increased antidonor CD8(+) cytotoxic T lymphocyte (CTL) and NK cell responses were observed. At this time, when recipient spleen cells were depleted of CD8(+) T cells and incubated with only donor platelets in 7-day antigen-presenting cell(APC) assays, enhanced proliferation and IL-2 production occurred. These cellular responses were not seen when 10(3) allogeneic leukocytes were transfused. Thus, the results suggest that leukoreduced platelet transfusions induce antidonor MHC antibodies and CD8(+) CTL responses in recipient mice. At the same time, the transfusions induced recipient CD4(+) T-cell activation when incubated with donor platelets in the presence of syngeneic APCs, an indirect recognition pathway that correlates with the time of alloantibody production. (C) 1995 by The American Society of Hematology.