CD1d-Restricted NKT Cells: An Interstrain Comparison

Hammond, Kirsten J. L.; Pellicci, Daniel G.; Poulton, Lynn D.; Naidenko, Olga V.; Scalzo, Anthony A.; Baxter, Alan G.; Godfrey, Dale I.

doi:10.4049/jimmunol.167.3.1164

Cited by 200 publications

(203 citation statements)

References 43 publications

(53 reference statements)

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“…iNKT cells are reduced in number in diabetes-prone NOD mice [4,5], and increasing the number of iNKT cells by adoptive transfer [6,7] or via the introduction of a Va14-Ja18 transgene, reduces significantly the progression of the disease [6]. A similar protection was observed after specific iNKT cell stimulation with exogenous ligands, a-galactosylceramide (a-GalCer) and its analogues [8][9][10][11].…”

Section: Introductionmentioning

confidence: 76%

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

et al. 2011

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Invariant natural killer T (iNKT) cells are a distinct lineage of innate-like T lymphocytes and converging studies in mouse models have demonstrated the protective role of iNKT cells in the development of type 1 diabetes. Recently, a new subset of iNKT cells, producing high levels of the pro-inflammatory cytokine IL-17, has been identified (iNKT17 cells). Since this cytokine has been implicated in several autoimmune diseases, we have analyzed iNKT17 cell frequency, absolute number and phenotypes in the pancreas and lymphoid organs in non-obese diabetic (NOD) mice. The role of iNKT17 cells in the development of diabetes was investigated using transfer experiments. NOD mice exhibit a higher frequency and absolute number of iNKT17 cells in the lymphoid organs as compared with C57BL/6 mice. iNKT17 cells infiltrate the pancreas of NOD mice where they express IL-17 mRNA. Contrary to the protective role of CD4 1 iNKT cells, the CD4 À iNKT cell population, which contains iNKT17 cells, enhances the incidence of diabetes. Treatment with a blocking anti-IL-17 antibody prevents the exacerbation of the disease. This study reveals that different iNKT cell subsets play distinct roles in the regulation of type 1 diabetes and iNKT17 cells, which are abundant in NOD mice, exacerbate diabetes development.

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Section: Introductionmentioning

confidence: 76%

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

et al. 2011

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“…When compared to NKT cell development in the mouse, the human thymus NKT cell compartment is more heavily skewed toward CD4 + cells. However, if CD161 -/low (NK1.1 -/low ) mouse NKT cells are examined, they too are predominantly CD4 + [13]. Therefore, one explanation may be the extent to which NKT cells differentiate in the human thymus, as more NKT cells reach CD161 + stages in the mouse thymus, often giving rise to CD4 -CD161 + NKT cells at a late stage in thymic NKT cell development [14].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have linked NKT cell deficiencies with cancer and autoimmune disease in humans [8][9][10][11], with a few exceptions [12]. In NKT cell-deficient NOD mice, the systemic NKT cell deficiency appears to originate in the thymus [13], but whether the highly variable frequency of NKT cells in human blood is also linked to NKT cell levels in the thymus is unknown, because no human studies have directly compared thymus and blood NKT cells from the same donors.…”

Section: Introductionmentioning

confidence: 99%

Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

et al. 2005

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NKT cells are a CD1d-restricted T cell subset with strong immunoregulatory properties. Human NKT deficiencies are associated with autoimmune diseases such as type 1 diabetes and several types of cancer, yet there is little understanding of how the human NKT cell pool develops or is maintained. In this study, we present the first detailed analysis of human NKT cells from donor-matched postnatal thymus and blood samples. In mice, NKT cells are a thymus-dependent population that migrates to the periphery at an immature stage. Our data show that human NKT cells also undergo early stages of development in the thymus, forming a CD4 + CD161 -/low population that predominates neonatal thymic and blood NKT cell pools. CD4 -and CD161 + NKT cells accumulate with age in the blood, but not thymus, to the point that they dominate the NKT cell compartment in adult blood. This is consistent with the post-thymic maturation of NKT cells exported from the thymus at the putatively immature CD4 + CD161 -/low stage. Interestingly, while thymus and peripheral NKT cell frequencies vary widely between patients and are relatively stable between age groups, there is no clear relationship between the NKT cell frequency in thymus and blood.

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“…Mononuclear cells were isolated from heparinized blood using lymphocyte separation medium (ICN Pharmaceutical). Lungs and livers were rinsed in PBS, diced with scissors, and gently pushed through a 40-m strainer with a syringe plunger (43). Lung suspensions were then washed with 40 ml of Click's Eagle-Hanks' amino acid medium and incubated for 30 min at 37°C in 20 ml of Click's medium containing 50 U/ml collagenase IV and 0.001% DNase I (Sigma-Aldrich; Ref.…”

Section: Preparation Of Cell Suspensions and Lymphocyte Recoverymentioning

confidence: 99%

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill

Keating

Yue

Rutigliano

et al. 2007

The Journal of Immunology

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Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8+ T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8+ T cells specific for the immunodominant H2DbNP366–374 (DbNP366) epitope. Functional analysis established that these liver-derived virus-specific CD8+ T cells are fully competent cytotoxic effectors and IFN-γ secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8+ T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8+ T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a “graveyard” for influenza virus-specific CD8+ T cells.

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CD1d-Restricted NKT Cells: An Interstrain Comparison

Cited by 200 publications

References 43 publications

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill

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