H-2 specific inotropic effect of alloimmune lymphoid cells on mouse isolated atria

Abstract

Alloimmunized lymphoid cells exert inotropic effects on isolated mouse atria. We here show that, when thymocytes were assayed on spontaneously beating isolated atria, a negative inotropic effect always appeared. When lymph node or spleen cells were assayed, they led to a biphasic effect: negative or positive inotropic effect, depending on the number of immunizations. Non-immunized lymphoid cells never exerted inotropic effects. Supernatants of alloimmunized cells cocultivated with pieces of atria from the immunizing strain exerted pharmacological effects on atria that mimicked those of whole cells. Inhibitors of lipoxygenase(s) and cyclooxygenase of arachidonic acid metabolism, inhibited the positive and negative inotropic effects, respectively. The specificity of the negative and positive inotropic effects, both in their induction and expression, was linked to the major histocompatibility complex. When T and B cells were purified from lymphoid tissues we found that they were responsible for the negative and positive inotropic effects on atria, respectively. Additionally, supernatants of T cells cultured with alloextracts triggered negative inotropic effects, but those from B cells were inactivated.