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.

Genetic studies with immunocompetent mice show the importance of both T cells and gamma interferon (IFN-␥A wide variety of RNA and DNA viruses, including measles virus (MV), West Nile virus (WNV), human immunodeficiency virus, human cytomegalovirus, herpes simplex virus type 1 (HSV-1) and HSV-2, rabies virus, poliovirus, and lymphocytic choriomeningitis virus, cross the blood-brain barrier, infect the central nervous system (CNS), and cause encephalitis in mammals (3,15,26,29,34,35,75,82,85). A suitable combination of host inflammatory factors and the blood-borne viral load enables most viruses to enter the CNS. However, in the vast majority of cases, neuronal infection does not lead to overt CNS disease (82). Viral encephalitis detection rates, even when symptoms are severe, are very low (46), due in part to the poor sensitivity of the tools used to detect infection (21). However, with the increase in the number of immunocompromised individuals, whether through increasing populations of AIDS patients or pharmacologically compromised tissue transplant recipients, there has been a concomitant increase in viral encephalitis (11,77). Some viral infections, rather than being cleared by the host's immune system, result instead in high morbidity or mortality, often accompanied by severe inflammation (18,68,81). The balance between whether the adaptive immune response to a specific viral infection is protective or harmful is delicate, as many of the mechanisms that mediate inflammation in the CNS in both settings are similar (6,12,31,65).MV infection manifests itself primarily as a childhood illness with a characteristic macropapular rash. Measles is associated with high morbidity and mortality in developing countries, mostly due to a transient immunosuppression that leaves infected individuals highly susceptible to secondary infections (61). In approximately 0.1% of the cases, MV also causes CNS complications; one of these, subacute sclerosing panencephalitis (SSPE), is a progressive fatal disease. MV-associated encephalitis is one of many viral brain infections that cause high morbidity and mortality (26,34,85). The delayed pathogenesis of SSPE, including the route of viral entry into the CNS, is poorly understood (49). Although it is widely accepted that MV infection in the brain leads to complications, this is not necessarily the case, as MV mRNA is detected in the brains of 20% of individuals with no CNS pathology (33,34). It is currently hypothesized that SSPE is a result of mutated, aberrant