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

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Abstract
4‐1BBL–/– 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 4‐1BB ligand (4‐1BBL) in vitro. To clarify the role of 4‐1BB/4‐1BBL in CD4+ versus CD8+ T cell responses in vivo, wecompared CD4 (OT‐II) and CD8 (OT‐I) TCR transgenic T cells responding to the same antigen in an in vivo adoptive transfer model in 4‐1BBL+/+ versus 4‐1BBL–/– mice. Duringprimary and secondary responses, expression of 4‐1BB on in vivo‐activated TCR transgenic T cells was earlier and more transient than previously observed in vitro, correlating withexpression of the early activation antigen CD69 and preceding the transition to the CD44hi state. Although 4‐1BB is expressed early in the primary response, there was no effect of 4‐1BBL deficiency on initial CD8 T cell expansion and only a minor effect on initial CD4 T cell expansion. The major effect of 4‐1BB/4‐1BBL interaction is on the T cell recall response. This is due to effects of 4‐1BBL on maintenance of T cell numbers at the end of the primary response with additional effects of 4‐1BBL on secondary expansion of T cells.