CD27 cooperates with the pre-T cell receptor in the regulation of murine T cell development

CD27 is a lymphocyte-specific member of the TNF receptor family and has a TNF-related transmembrane ligand, CD70. The CD27/CD70 receptor-ligand pair cooperates with the TCR in the regulation of the peripheral T cell response. The study presented here reveals that CD27 may play a similar role in thymic pre-T cell development. We have previously cloned the cDNA encoding murine CD27, prepared specific mAbs and observed that murine CD27 is expressed on virtually all thymocytes, with the exception of a subpopulation of CD4(-)8(-) precursor T cells. It is shown here that induction of murine CD27 expression occurs at the transition from the CD4(-)8(-)25(+) to the CD4(-)8(-)25(-) precursor T cell stage and is regulated by the pre-TCR. Therefore, we investigated whether CD27 contributes to pre-TCR-mediated thymocyte development. Pre-TCR function was mimicked by the induction of CD3 signaling in thymocytes of recombination activating gene (RAG)-deficient mice. This in vivo anti-CD3 epsilon mAb treatment induces an about fifty fold numerical expansion of CD4(-)8(-)25(+) thymocytes and their differentiation to the CD4(+)8(+)25(-) stage. Co-injection of anti-CD27 mAb inhibited the CD3-mediated. expansion and differentiation of the CD4(-)8(-)25(+) precursor population. Also, injection of anti-CD27 mAb in TCR alpha(-/-) mutant mice led to a reduction in the absolute number- of CD4(+)8(+)25(-) thymocytes. The present evidence that in these in vivo systems, anti-CD27 mAb inhibits CD27-ligand interaction. Therefore, we conclude that CD27 may contribute to normal murine T cell development by synergizing with the pre-TCR-mediated signal.