Increase of CD4+TNFα+IL-2−T cells in cerebrospinal fluid of multiple sclerosis patients

Abstract

Intracellular production of TNFalpha and IL-2 after stimulation with phorbol myristate/ionomycin was flowcytometrically measured in CD4(+) T cells from peripheral blood (PB) and cerebrospinal fluid (CSF) of 29 patients with multiple sclerosis (MS), and 16 with other inflammatory and 41 with other non-inflammatory neurological diseases. In CSF, the percentages of CD4(+)TNFalpha(+)IL-2(-)T cells were significantly higher in patients with MS than either of the controls, whereas no difference was found in CD4(+)TNFalpha(+)IL-2(+)T or CD4(+)TNFalpha(-)IL-2(+)T cells. The increase was more pronounced at relapse than in remission. No significant change was detected in PB. These findings suggested that CD4(+)TNFalpha(+)IL-2(-)T cells are intrathecally upregulated in MS.

Nanowire array chips for molecular typing of rare trafficking leukocytes with application to neurodegenerative pathology

“…Enumeration of the captured cells showed increased frequency of both CD4+ and CD8+ T cells (Table 1). Our observation again agrees with previous findings showing increases of CD4+ T cells in CSF of inflammatory diseases in the CNS 71,72 . Increases of CD4+ T cells in CSF, which can assume a helper–I T cell phenotype and secrete pro-inflammatory cytokines, may indicate brain inflammation and related neuronal damage 73 .…”

“…Our preliminary study showed that the total trafficking leukocyte counts in AD patients’ CSF modestly increased compared to normal CSF leukocyte counts. An increased frequency of both CD4+ and CD8+ T cells was observed, which agrees with previous findings that there are elevations of both T cell subsets in the brain of neurodegenerative disease 71,72 . AD patients exhibited significantly altered profiles of leukocyte phenotypes, confirming the recent notion that the increased migration of CD8+ cytotoxic T cells is associated with AD development.…”

Inflammatory Cytokine Induced Regulation of Superoxide Dismutase 3 Expression by Human Mesenchymal Stem Cells

“…Inflammatory processes within the CNS involve activated microglia, astrocytes, macrophages and lymphocytes releasing a plethora of anti-and pro-inflammatory cytokines including both IFN-gamma and TNF-alpha [43]. This occurs in a number of inflammatory neurodegenerative disorders, including multiple sclerosis, in which high levels of TNF-alpha within cerebrospinal fluid and infiltration of IFN-gamma secreting activated T-cells into the brain is seen [44][45][46]. Neuroinflammation and subsequent microglial activation plays an important role in the pathogenesis of several neurodegenerative disorders.…”

Akt Fine-tunes NF-κB-dependent Gene Expression during T Cell Activation

“…Production of TNF-␣ by bone marrow T cells has been linked to bone loss associated with estrogen deficiency (36,37). In addition, the presence of TNF-␣-producing T cells correlates with disease severity and progression in multiple sclerosis (38,39). Finally, the production of TNF-␣ by alloreactive T cells was shown to predict allograft rejection (40).…”