CD8+ T cell activation correlates with disease activity in clinically isolated syndromes and is regulated by interferon-β treatment

Jensen, Jan H.; Langkilde, Annika Reynberg; Frederiksen, Jette Lautrup; Sellebjerg, Finn

doi:10.1016/j.jneuroim.2006.06.024

Cited by 16 publications

(15 citation statements)

References 79 publications

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“…IFN-β has previously been reported to induce the expression of activation markers on CD8+ T cells in MS [21], [25]. This is consistent with the results of studies demonstrating that type I IFN can enhance antiviral cytotoxic T cell and NK cell responses, i.e., an immune activating effect of type I IFN [1], [26].…”

Section: Discussionsupporting

confidence: 87%

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Endogenous and Recombinant Type I Interferons and Disease Activity in Multiple Sclerosis

et al. 2012

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Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26high T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26high T cells, and the percentage of CD4+CD26high T cells that were CD49dhigh correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

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Section: Discussionsupporting

confidence: 87%

“…The sample size was based on previous studies on the effects of IFN-β in small patient cohorts and on studies reporting that gene expression profiling in 22 MS patients could identify subgroups with different disease courses during treatment with IFN-β [19]–[21]. Values are given as median with inter-quartile range.…”

Section: Methodsmentioning

confidence: 99%

Endogenous and Recombinant Type I Interferons and Disease Activity in Multiple Sclerosis

et al. 2012

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“…Interestingly, the immune cell population in canine CAFRs was dominated by increased numbers of CD3 (Hennino et al, 2007). In addition, under different circumstances CD8 + T cells are able to express IL-10, TGF-b, IL-4, IL-13, Foxp3, and IFN-c (Teraki et al, 2000;Berg et al, 2002;Jensen et al, 2006;Mahic et al, 2008). In canine AD an increased presence of CD4 + and CD8 + T cells in LS skin is reported, but the ratio of CD4 + /CD8 + T cells measured in the epidermis is debated.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of T cell phenotypes, cytokines and transcription factors in the skin of dogs with cutaneous adverse food reactions

Veenhof

Knol

Schlotter

et al. 2011

The Veterinary Journal

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a b s t r a c tThe immunopathogenesis of cutaneous adverse food reactions (CAFRs) in dogs is unknown. Since the clinical manifestations in the skin are like those found in canine atopic dermatitis (AD), this study investigated the similarity in T cell phenotypes and gene expression of cytokines and transcription factors in CAFRs. In addition, the influence of an elimination diet on these parameters was tested.In the skin of canine CAFRs, a predominant presence of CD8 + T cells and increased expression of the IL-4, IL-13, Foxp3 and SOCS-3 genes were observed. IFN-c gene expression was increased in lesional compared to non-lesional skin. The predominance of CD8 + T cells indicates that the immunopathogenesis of CAFRs is different from that of canine AD. The elimination diet relieved clinical signs, but did not influence T cell phenotypes or expression of the cytokine and transcription factor genes in the skin of dogs with CAFRs, indicating a continuously pre-activated immune status in dogs sensitised to food constituents.

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“…CD26 expression has previously been reported in multiple inflammatory conditions and linked to inflammatory Th1 cells in the pre-Th17 era (9). CD26 upregulation correlates with disease activity in human autoimmune diseases such as rheumatoid arthritis (10) and multiple sclerosis (11)(12)(13), diseases that have recently been linked to the presence of pathogenic Th17 cells. However, whether CD26 expression is linked to a specific subset of inflammatory T cells, such as Th17 cells, has not been previously addressed.…”

mentioning

confidence: 97%

Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)

Bengsch

Seigel

Flecken

et al. 2012

The Journal of Immunology

153

163

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Dipeptidylpeptidase IV (CD26) is a multifunctional ectoenzyme involved in T cell activation that has been implicated in autoimmune pathophysiology. Because IL-17–producing CD4+ T cells (Th17 cells) are important mediators of autoimmune disease, we analyzed the expression of CD26 and its enzymatic function on human Th17 cells. Analysis of CD26 expression on different CD4+ T helper subsets showed that CD26 expression is highest on CD4+ T cells producing type 17 cytokines (e.g., IL-22, IL-17, GM-CSF, or TNF) compared with Th1, Th2, and regulatory T cells. Phenotypic analysis revealed that CD26++CD4+ T cells express the type 17 differentiation molecules CD161, CCR6, lL-23R, and retinoic acid-related orphan receptor-γt. Furthermore, sorted CD26++CD4+ T cells contain >90–98% of Th17 cells, indicating that CD26++ T cells harbor the Th17 lineage. A comparison with CD161 and CCR6 indicated that analysis of CD26 coexpression may improve the phenotypic characterization of Th17 cells. Of note, CD26++ Th17 cells are enriched in the inflamed tissue of patients with hepatitis and inflammatory bowel disease. Functional analysis in migration assays revealed that CD26 expressed on Th17 cells is enzymatically active. Indeed, CD26 negatively regulates the chemotactic CD4+ T cell response to the inflammatory chemokines CXCL9–12 that can be restored by pharmacological blockade of the enzymatic center of CD26. In summary, these results strongly suggest that CD26 may contribute to the orchestration of the immune response by Th17 cells in human inflammatory diseases. They also suggest that the phenotypic analysis of Th17 cells may be facilitated by determination of CD26 expression.

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CD8+ T cell activation correlates with disease activity in clinically isolated syndromes and is regulated by interferon-β treatment

Cited by 16 publications

References 79 publications

Endogenous and Recombinant Type I Interferons and Disease Activity in Multiple Sclerosis

Endogenous and Recombinant Type I Interferons and Disease Activity in Multiple Sclerosis

Characterisation of T cell phenotypes, cytokines and transcription factors in the skin of dogs with cutaneous adverse food reactions

Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)

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