Expression and function of 4-1BB during CD4 versus CD8 T cell responses in vivo

4-1 BBL-/- mice have a defect in recall CD8(+) T cell responses to viruses, whereas CD4(+) T cell responses to virus are unimpaired in these mice. In contrast, both CD4(+) and CD8(+) T cells respond to 4-1 BB ligand (4-1 BBL) in vitro, To clarify the role of 4-1 BB/4-1 BBL in CD4(+) versus CD8(+) T cell responses in vivo, we compared CD4 (OT-II) and CD8 (OT-I) TCR transgenic T cells responding to the same antigen in an in vivo adoptive transfer model in 4-1 BBL+/+ versus 4-1 BBL-/- mice. During primary and secondary responses, expression of 4-1 BB on in vivo-activated TCR transgenic T cells was earlier and more transient than previously observed in vitro, correlating with expression of the early activation antigen CD69 and preceding the transition to the CD44(hi) state. Although 4-1 BB is expressed early in the primary response, there was no effect of 4-1 BBL deficiency on initial CD8 T cell expansion and only a minor effect on initial CD4 T cell expansion. The major effect of 4-1 BB/4-1 BBL interaction is on the T cell recall response. This is due to effects of 4-1 BBL on maintenance of T cell numbers at the end of the primary response with additional effects of 4-1 BBL on secondary expansion of T cells.