Inflammatory bowel disease (IBD) is characterized by damage to the gut mucosa and systemic inflammation. We sought to evaluate the role of chronic inflammation on circulating T-cell activation in human subjects with Crohn's disease and ulcerative colitis. We studied 54 patients with IBD and 28 healthy controls. T-cell activation and cycling were assessed in whole blood samples by flow cytometry. Levels of lipopolysaccharide (LPS) were measured in serum by Limulus amoebocyte lysate assay, and plasma levels of inflammatory markers and LPS-binding proteins were measured by ELISA. The proportions of circulating CD4(+) and CD8(+) T lymphocytes in cycle (Ki67(+) ) are increased in patients with IBD compared with these proportions in controls. CD8(+) T cells from patients with IBD are also enriched for cells that expressed CD38 and HLA-DR, and proportions of these cells are related to plasma levels of interleukin-6 and C-reactive protein in these patients. Intracellular interleukin-2 and interferon-γ levels were elevated in resting and polyclonally activated CD4(+) and CD8(+) T cells in patients with IBD when compared with levels from healthy controls. Surprisingly, we did not find increased levels of LPS in the serum of patients with IBD. We did, however, find a signature of recent microbial translocation, as levels of LPS-binding protein are increased in the plasma of patients with IBD compared with plasma levels in healthy controls; LPS-binding protein levels are also directly related to proportions of CD38 HLA-DR-expressing CD4(+) and CD8(+) T cells. Local damage to the gastrointestinal tract in IBD may result in systemic inflammation and T-cell activation.

To examine heterogeneity in dendritic cell (DC) antigen presentation function, murine splenic DCs were separated into CD4+ and CD8+ populations and assessed for the ability to process and present particulate antigen to CD4+ and CD8+ T cells. CD4+ and CD8+ DCs both processed exogenous particulate antigen, but CD8+ DCs were much more efficient than CD4+ DCs for both major histocompatibility complex (MHC) class II antigen presentation and MHC class I cross-presentation. While antigen processing efficiency contributed to the superior antigen presentation function of CD8+ DCs, our studies also revealed an important contribution of CD24. CD8+ DCs were also more efficient than CD4+ DCs in inducing naïve T cells to acquire certain effector T-cell functions, for example generation of cytotoxic CD8+ T cells and interferon (IFN)-gamma-producing CD4+ T cells. In summary, CD8+ DCs are particularly potent antigen-presenting cells that express critical costimulators and efficiently process exogenous antigen for presentation by both MHC class I and II molecules.