Frequency and function of circulating invariant NKT cells in autoimmune diabetes mellitus and thyroid diseases in Colombian patients

Román-Gonzaléz, Alejandro; Moreno, María Eugenia; Alfaro, Juan Manuel Esquivel; Uribe, Federico; Latorre-Sierra, Guillermo; Rugeles, Marı́a Teresa; Montoya, Carlos

doi:10.1016/j.humimm.2009.01.012

Cited by 25 publications

(19 citation statements)

References 37 publications

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“…This is an area of controversy; for example, we and others have seen no clear association with NKT cell numbers (66)(67)(68)(69)(70) and increased numbers have been reported (71,72).…”

Section: Discussionmentioning

confidence: 69%

Role of SLAM in NKT Cell Development Revealed by Transgenic Complementation in NOD Mice

Jordan

Fletcher

Jose

et al. 2011

The Journal of Immunology

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Allelic variation of SLAM expression on CD4+CD8+ thymocytes has been proposed to play a major role in NKT cell development. In this article, this hypothesis is tested by the production of subcongenic mouse strains and Slamf1 transgenic lines. The long isoform of the C57BL/6 allele of Slamf1 was transgenically expressed on CD4+CD8+ thymocytes under control of an hCD2 minigene. NOD.Nkrp1b.Tg(Slamf1)1 mice, which had a 2-fold increase in SLAM protein expression on CD4+CD8+ thymocytes, had a 2-fold increase in numbers of thymic NKT cells. The additional thymic NKT cells in NOD.Nkrp1b.Tg(Slamf1)1 mice were relatively immature, with a similar subset distribution to those of congenic NOD.Nkrp1b.Nkt1 and NOD.Nkrp1b.Slamf1 mice, which also express increased levels of SLAM on CD4+CD8+ thymocytes and produce larger numbers of NKT cells. Transgenic enhancement of SLAM expression also increased IL-4 and IL-17 production in response to TCR-mediated stimulation. Paradoxically, NOD.Nkrp1b.Tg(Slamf1)2 mice, which had a 7-fold increase in SLAM expression, showed no significant increase in NKT cells numbers; on the contrary, at high transgene copy number, SLAM expression levels correlated inversely with NKT cell numbers, consistent with a contribution to negative selection. These data confirm a role for SLAM in controlling NKT cell development and are consistent with a role in both positive and negative thymic selection of NKT cells.

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“…This is an area of controversy; for example, we and others have seen no clear association with NKT cell numbers (66)(67)(68)(69)(70) and increased numbers have been reported (71,72).…”

Section: Discussionmentioning

confidence: 69%

Role of SLAM in NKT Cell Development Revealed by Transgenic Complementation in NOD Mice

Jordan

Fletcher

Jose

et al. 2011

The Journal of Immunology

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“…Early studies indicated that frequencies of iNKT-cells were reduced in T1D patients and functionally they were altered with an impaired ability to produce Th2 cytokines 30, 31 . However, these observations were later challenged by others as the numerical and functional differences between iNKT-cells in human T1D patients and control subjects were not consistently reported 9, 32 . It has also been reported that while no differences were found in the frequencies of total iNKT-cells, the proportions of the CD4 + subset were significantly reduced in humans with or at high risk for T1D 6, 7 .…”

Section: Introductionmentioning

confidence: 99%

Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions

et al. 2013

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Reduced frequency of invariant natural killer T (iNKT)-cells has been indicated as a contributing factor to type 1 diabetes (T1D) development in NOD mice. To further understand the genetic basis of the defect, we generated (NOD X ICR)F2 mice to map genes that control iNKT-cell development. We determined frequencies of thymic and splenic iNKT-cells as well as the ratio of CD4-positive and -negative subsets in the spleens of 209 F2 males. Quantitative trait loci (QTL) analysis revealed 5 loci that exceed the significant threshold for the frequency of thymic and/or splenic iNKT-cells on Chromosomes (Chr) 1, 5, 6, 12, and 17. Three significant loci on Chr 1, 4, and 5 were found for the ratio of CD4-positive and -negative splenic iNKT-cells. Comparisons to previously known mouse T1D susceptibility (Idd) loci revealed two significant QTL peak locations respectively mapped to Idd regions on Chr 4 and 6. The peak marker location of the significant Chr 12 iNKT QTL maps to within 0.5Mb of a syntenic human T1D locus. Collectively, our results reveal several novel loci controlling iNKT-cell development and provide additional information for future T1D genetic studies.

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“…Early studies indicated that frequencies of iNKT-cells were reduced in T1D patients and functionally they were altered with an impaired ability to produce Th2 cytokines 20, 21 . However, these observations were later challenged by others as the numerical and functional differences between iNKT-cells in human T1D patients and control subjects were not consistently reported 22, 23 . It has also been reported that while no differences were found in the frequencies of total iNKT-cells, the proportions of the CD4 + subset were significantly reduced in humans with or at high risk for T1D 24, 25 .…”

Section: Introductionmentioning

confidence: 99%

Genetic control of murine invariant natural killer T-cell development dynamically differs dependent on the examined tissue type

2011

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Previous studies using gene-targeted mutant mice revealed several molecules important for the development or function of invariant natural killer (iNKT)-cells. However, these gene knockout mice represent cases that are rare in humans. Thus, it remains unclear how naturally occurring allelic variants of these genes or others regulate the numerical and functional diversity of iNKT-cells in both mice and humans. Studies in humans are mostly limited to iNKT-cells in peripheral blood (PB). It is not known if the relative distribution of iNKT-cells between PB and other lymphoid organs is correlated or under common genetic control. To initially address these questions, we analyzed iNKT-cells in the spleen, thymus, and PB of 38 inbred mouse strains. Percentages of iNKT-cells in these three anatomical sites varied significantly in a strain-dependent manner. The correlation between PB and spleen was moderate, and none was observed between PB and thymus. Similarly, proportions of the CD4-expressing subset of iNKT-cells differed significantly among inbred strains. The percentages of CD4-positive iNKT-cells displayed a strong correlation between PB and spleen although it remained poor between PB and thymus. Genome-wide association studies across strains identified only partially overlapping loci associated with variability of iNKT-cell frequencies within and between differing anatomical sites.

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Frequency and function of circulating invariant NKT cells in autoimmune diabetes mellitus and thyroid diseases in Colombian patients

Cited by 25 publications

References 37 publications

Role of SLAM in NKT Cell Development Revealed by Transgenic Complementation in NOD Mice

Role of SLAM in NKT Cell Development Revealed by Transgenic Complementation in NOD Mice

Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions

Genetic control of murine invariant natural killer T-cell development dynamically differs dependent on the examined tissue type

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