Influence of T cell-expressed CD83 on the regulation of immune responses
The glycoprotein CD83 is a classical marker for mature DCs, but it is also expressed on the surface of many other cell types including activated B and T cells. Increasing evidence indicates that CD83 expression on T cells contributes to the regulation of T cell activation and immune responses in general. However, the precise function of T cell-expressed CD83 is still elusive. Therefore, we carefully investigated the role of CD83 expression in T cells in the present study. Herein, we identified CD83 to be expressed on regulatory (Treg) as well as conventional (Tconv) T cells upon stimulation. To better define the role of naturally expressed CD83 on T cells, we generated a T cell-specific CD83 conditional knockout mouse (CD4KO). CD4KO mice showed the same numbers and frequencies of CD4+ T cells in the thymus and different secondary lymphoid organs, indicating that T cell-specific CD83 expression has no impact on T cell development. Furthermore, T cell-specific CD83 deletion did neither affect Treg cell induction nor Treg cell inhibitory function in vitro. In contrast, Tconv cells from CD4KO mice depicted a significantly altered phenotype. Upon in vitro stimulation naive CD4+ Tconv cells from CD4KO mice showed significantly enhanced activation, elevated proliferation as well as increased TH1 cell differentiation compared to Tconv cells from CD4WT mice. In addition, CD83-deficient Tconv cells showed significantly enhanced phosphorylation of ZAP-70 compared to CD4WT Tconv cells upon in vitro stimulation, suggesting a regulation of TCR signaling by CD83. In vivo CD4KO mice developed a more severe CHS reaction compared to CD4WT mice, which was accompanied by significantly increased activation and proinflammatory cytokine secretion of CD83-deficient CD4+ T cells. Moreover, CD83 deletion in CD4+ T cells led to exacerbated T cell transfer induced colitis in Rag2KO mice compared to the transfer of wildtype CD4+ T cells, demonstrating an important role of cell-intrinsic CD83 expression in Tconv cell function. In addition to the cell-intrinsic effects, T cell-specific CD83 deletion induced elevated DC activation in vitro and in vivo suggesting a cell-extrinsic function of T cell-expressed CD83 expression in regulation of T cell activation as well. In summary, we showed for the first time that CD83 expressed on stimulated Tconv cells negatively regulates T cell activation by cell-intrinsic as well as cell-extrinsic mechanisms.