We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help.

CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer.

CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of CD40^+/+ CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with CD40^+/+ CD4 T cells. Adoptive transfer of CD40L^+/+ CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of CD40L^+/+ CD4 T cells was required even for memory CD8 T cells response to H60.

Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to naïve and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.