Multiple immuno-regulatory defects in type-1 diabetes

Kukreja, Anjli; Cost, Giulia; Marker, John; Zhang, Chenhui; Sun, Zhong Sheng; Lin‐Su, Karen; Ten, Svetlana; Sanz, Maureen M.; Exley, Mark A.; Wilson, Brian; Porcelli, Steven A.; Maclaren, Noel K.

doi:10.1172/jci13605

Cited by 214 publications

(63 citation statements)

References 67 publications

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“…On the other hand, this kind of immunoenhanching effect may result in the induction of regulatory mechanisms. Decreased activation of IFN-g response has been associated with atopic diseases [45] as well as with autoimmune diseases [46,47]. Physiological maturation of the immune system during childhood includes increased production of IFN-g [48].…”

Section: Effect Of Probiotics On the Innate Immune Systemmentioning

confidence: 99%

Immunological effects of probiotics with special reference to lactobacilli

Vaarala¹

2003

Clin Experimental Allergy

108

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Section: Effect Of Probiotics On the Innate Immune Systemmentioning

confidence: 99%

Immunological effects of probiotics with special reference to lactobacilli

Vaarala¹

2003

Clin Experimental Allergy

108

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“…As opposed to animal models, it is still unclear how nTreg contribute to the development of human autoimmune disease. Autoimmune diabetes was the first example where decreased frequency of peripheral nTreg was reported as a potential indicator for the impaired state of peripheral tolerance to islet antigens [4]. However, available data on the frequency of nTreg in the peripheral blood of MS patients has so far not revealed significant differences [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients

Feger

Luther

Poeschel

et al. 2007

Clinical and Experimental Immunology

180

127

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Summary Naturally occurring CD4+ CD25 + regulatory T cells (nTreg) play a major role in controlling autoimmunity by suppressing self-reactive T cells. Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS), where T cells play a key role in orchestrating tissue damage. While CD4 + CD25 + nTreg have been investigated in peripheral blood from MS patients, little is known about their presence and possible function within the target organ, the CNS. In order to study whether these cells are present in the cerebrospinal fluid (CSF) under pathological conditions, we have analysed the frequency of CD4 + CD25 + nTreg in peripheral blood and CSF from MS patients (n = 14), patients with other neurological disorders (OND; n = 9) and compared peripheral levels with healthy controls (n = 40). We found that the frequency of CD4 + CD25 + forkhead transcription factor 3 (FOXP3) + nTreg was significantly elevated in the CSF from MS patients (mean CSF = 4·05 Ϯ 1·54% versus mean peripheral blood = 2·93 Ϯ 0·94%) but not from patients with other neurological disorders (mean CSF = 3·78 Ϯ 1·26% versus mean peripheral blood = 3·74 Ϯ 1·4%). The frequency of nTreg in the periphery did not differ between MS patients and healthy donors; however, nTreg from MS patients showed reduced suppressive capacity.

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“…The presence and effect of a defective NKT population is less clear when studied in humans (62,63). However, in these experiments the measurements were taken from the blood rather than the pancreatic lymph nodes, and a locally defective population of NKT cells cannot be excluded.…”

Section: Research On T1d and Nkt Cellsmentioning

confidence: 98%

The preventive role of type 2 NKT cells in the development of type 1 diabetes

Sørensen

Buschard

Brogren

2013

APMIS

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In the last two decades, natural killer T (NKT) cells have emerged as an important factor in preventing type 1 diabetes (T1D) when investigated in the experimental non-obese diabetic (NOD) mouse model. So far, investigations have largely focused on type 1 NKT cells with invariant T-cell receptors, whereas the role of type 2 NKT cells with diverse T-cell receptors is less well understood. However, there have been several findings which indicate that in fact type 2 NKT cells may regulate the progression of type 1 diabetes in NOD mice, including a fraction of these cells which recognize β-cell-enriched sulfatide. Therefore, the focus for this review is to present the current evidence of the effect of type 2 NKT cells on the development of T1D. In general, there is still uncertainty surrounding the mechanism of activation and function of NKT cells. Here, we present two models of the effector mechanisms, respectively, Th1/Th2 polarization and the induction of tolerogenic dendritic cells (DC). In conclusion, this review points to the importance of immunoregulation by type 2 NKT cells in preventing the development of T1D and highlights the induction of tolerogenic DC as a likely mechanism. The possible therapeutic role of type 1 and type 2 NKT cells are evaluated and future experiments concerning type 2 NKT cells and T1D are proposed.

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Multiple immuno-regulatory defects in type-1 diabetes

Cited by 214 publications

References 67 publications

Immunological effects of probiotics with special reference to lactobacilli

Immunological effects of probiotics with special reference to lactobacilli

Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients

The preventive role of type 2 NKT cells in the development of type 1 diabetes

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