Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations.

OX40/OX40 ligand (OX40L) interactions are implicated in costimulation for both CD4(+) T and B cells in a bidirectional manner. To determine the role of OX40/OX40L interactions in recipient antidonor responses after multiple allogeneic transfusions, we examined alloreactive cytotoxic T lymphocyte (allo-CTL) activity and alloantibody production in repeatedly alloimmunized OX40L-deficient mice. After the fifth alloimmunization, whereas OX40L-deficient mice showed allo-CTL activity with levels comparable to those of wild-type mice, alloantibody production in OX40L-deficient mice was significantly reduced, accompanied by fewer memory B and CD4(+) T cells with reduced function. Furthermore, nu/nu mice that received OX40L-deficient T cells still exhibited impaired alloantibody production with fewer memory CD4(+) T and B cells. In contrast, RAG-2-deficient mice that received both wild-type T cells and OX40L-deficient B cells produced scant alloantibodies with fewer memory B cells, but sufficient memory CD4(+) T cells. Thus, OX40L on B cells, rather than on T cells, is apparently required for adequate and persistent production of alloantibodies after repeated alloimmunizations.