Circulating CD4⁺ and CD8⁺ T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation

Abstract

SummaryInflammatory 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-c 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.

Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function

“…Indeed, inflammatory bowel disease (IBD), which is classically defined as chronic uncontrolled intestinal inflammation, can be characterized by elevated frequencies of activated T cells, including Th17 cells, in the intestine (36, 37) and increased percentages of activated and proliferating T cells in the periphery (38). In addition, it is well established that activated CD4+ T cells are the preferential targets of HIV (39) and the high prevalence of these cells in the GI tract causes this tissue to experience the greatest CD4+ T cell loss during progressive HIV infection and become a reservoir for HIV replication (40, 41).…”

Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease

“…Expression of TXK, a member of the Tec family of non-receptor tyrosine kinases, in Th1 T cells is obligatory for the production of interferon gamma44. CD8 + T cells have an established role in IBD pathogenesis284546 with recent data suggesting that CD8 + T cell exhaustion may be a critical prognostic factor in immune-mediated diseases47.…”

Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation

“…In patients with IBD, immune cell infiltrates are increased in the intestinal mucosa (5,21), and plasma cell and T-lymphocyte numbers are increased in the lamina propria (21,39). Lymphocytes and macrophages secrete Ucn1, and specific immune cells express its receptor, CRF 2 , after activation by lipopolysaccharides and glucocorticoids (34).…”