CD8+Foxp3+ T cells in peripheral blood of relapsing-remitting multiple sclerosis patients

Frisullo, Giovanni; Nociti, Viviana; Iorio, Raffaele; Plantone, Domenico; Patanella, Agata Katia; Tonali, P.; Batocchi, Anna Paola

doi:10.1016/j.humimm.2010.01.024

Cited by 44 publications

(37 citation statements)

References 31 publications

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“…The question occurs whether differences observed in this study are caused by differences in frequency of this specific subset. Note that no numerical differences in CD8 regulatory T cells between MS patients and HC have been described (32), nor have functional defects in this subset been shown (33). Although we previously found a significant increased frequency of CD8 regulatory T cells coexpressing IL-7Ra in MS patients (34), this increase was only ∼5% of the total increase in IL-7Ra expression on CD8 T cells observed in this study.…”

Section: Discussioncontrasting

confidence: 67%

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Kreft

Verbraak

Wierenga‐Wolf

et al. 2012

The Journal of Immunology

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The IL-7Rα single nucleotide polymorphism rs6897932 is associated with an increased risk for multiple sclerosis (MS). IL-7Rα is a promising candidate to be involved in autoimmunity, because it regulates T cell homeostasis, proliferation, and antiapoptotic signaling. However, the exact underlying mechanisms in the pathogenesis of MS are poorly understood. We investigated whether CD4 and CD8 lymphocyte subsets differed in IL-7Rα expression and functionality in 78 MS patients compared with 59 healthy controls (HC). A significantly higher frequency of IL-7Rα+ CD8 effector memory (CD8EM) was found in MS. Moreover, IL-7Rα membrane expression was significantly increased in MS in naive and memory CD8 (all p < 0.05) with a similar trend in CD8EM (p = 0.055). No correlation was found between the expression level or frequency of IL-7Rα+CD8+ and rs6897932 risk allele carriership. Upon IL-7 stimulation, MS patients had stronger STAT5 activation in CD8EM compared with HC. IL-7 stimulation had a differential effect on both mRNA and protein expression of granzyme A and granzyme B between MS and HC. Stainings of different lesions in postmortem MS brain material showed expression of IL-7 and CD8+IL-7Rα+ in preactive, but not in active, demyelinating MS lesions, indicating involvement of IL-7Rα+ lymphocytes in lesion development. The intralesional production of IL-7 in combination with the lower threshold for IL-7–induced cytotoxicity in MS may enhance the pathogenicity of these CD8 T cells. This is of special interest in light of the established demyelinating and cytotoxic actions of granzyme A.

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Section: Discussioncontrasting

confidence: 67%

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Kreft

Verbraak

Wierenga‐Wolf

et al. 2012

The Journal of Immunology

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“…The paper mentions the significance of immunological vigilance and the fact that CD8 Treg may promote tumoral growth. It also describes this cell subpopulation in patients with multiple sclerosis in whom lower numbers of these cells were correlated with relapse, a fact that may evidence their immunosuppressant role in the control of autoimmune diseases (Giovanni Frisullo, 2010;Chaput, 2009;Kiniwa, 2007). Recently described populations of CD8+ Treg include CD8+ IL-10+ cells present in ovarian carcinoma, which are induced by plasmocytoid dendritic cells infiltrating the tumor.…”

Section: Clinical Relevance Of Regulation and Induction Of Tolerance mentioning

confidence: 96%

Determination of Th1/Th2/Th17 Cytokines in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Gutiérrez‐Hoya¹,

López‐Santiago²,

Vela‐Ojeda³

et al. 2012

New Advances in Stem Cell Transplantation

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“…This enables the CD8+ cells to acquire suppressive activity. Relapsing MS patients have lower percentages of circulating CD8+Foxp3+ T cells compared with remitting MS patients and healthy subjects, suggesting that these cells maintain tolerance in MS 51. CD8+ CD25+ FoxP3+ cells also mediate inhibition of IFN‐ γ and IL‐17 secretion.…”

Section: Immunopathogenesismentioning

confidence: 99%

Immunologic Aspects of Multiple Sclerosis

Boppana¹,

Huang²,

Ito³

et al. 2011

Mount Sinai J Medicine

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Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system characterized by demyelination and axonal loss. Genetic and environmental factors contribute to the risk of immune dysregulation in multiple sclerosis. The review focuses on the immunopathogenic role played by various lymphocyte subsets and their cytokine products in the onset and disease progression, and the role of regulatory immune cells in disease remission. The mechanism of action of approved and experimental therapies, and how these mechanisms support the immunopathogenesis paradigm, is also reviewed.

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CD8+Foxp3+ T cells in peripheral blood of relapsing-remitting multiple sclerosis patients

Cited by 44 publications

References 31 publications

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Determination of Th1/Th2/Th17 Cytokines in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Immunologic Aspects of Multiple Sclerosis

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