Although induction of CD8 T-cell responses to transplants requires CD4-cell help, how this help is transmitted remains incompletely characterized. In vitro, cognate interactions between CD4 T cells and dendritic cells (DCs) induce C3a and C5a production. CD8⁺ T cells lacking C3a receptor (C3aR) and C5a receptor (C5aR) proliferate weakly to allogeneic DCs despite CD4 help, indicating that CD4-cell help is mediated, in part, through DC-derived C3a/C5a acting on CD8⁺ T cell–expressed C3aR/C5aR. In support of this concept, augmenting DC C5a/C3a production bypasses the requirement for CD4- and CD40-dependent help to wild-type CD8⁺ T cells. CD4-deficient recipients of allogeneic heart transplants prime weak CD8 responses and do not acutely reject their grafts. In contrast, CD4-deficient chimeric mice possessing decay accelerating factor deficient (Daf1^−/−) bone marrow, in which DC C3a/C5a production is potentiated, acutely reject transplants through a CD8 cell–dependent mechanism. Furthermore, hearts transplanted into CD40^−/− mice prime weak CD8-cell responses and survive indefinitely, but hearts transplanted into Daf1^−/−CD40^−/− recipients undergo CD8 cell–dependent rejection. Together, the data indicate that heightened production and activation of immune cell–derived complement bypasses the need for CD40/CD154 interactions and implicate antigen-presenting cell–produced C5a and C3a as molecular bridges linking CD4 help to CD8⁺ T cells.