Genetic Linkage of Thymic T-Cell Proliferative Unresponsiveness to Mouse Chromosome 11 in NOD Mice: A Possible Role for Chemokine Genes

Gill, Bruce M.; Jaramillo, Andrés; Ma, Lingli; Laupland, Kevin B.; Delovitch, Terry L.

doi:10.2337/diab.44.6.614

Cited by 20 publications

(10 citation statements)

References 24 publications

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“…It was reported that NOD mice have a defect in the TCR signaling cascade mediated through the protein kinase C/Ras/MAPK pathway (16)(17)(18). This NOD-specific trait, manifested by T cell hyporesponsiveness with reduced IL-2 and -4 secretion, was genetically mapped to gene(s) in the Idd4.2 region on chromosome 11 (39,40). The fact that the B6 allele of the Ctex/Cd3z region only partially restored the B6 IL-2 and IFN-g cytokine expression pattern and proliferation profile is compatible with a complementary function of the Idd4 and Ctex/Cd3z genes.…”

Section: Discussionmentioning

confidence: 99%

“…RNA concentrations were measured using a Nanodrop spectrophotometer, and cDNA was prepared from 300 ng total RNA using the Reverse Transcription Reagents (TaqMan, Applied Biosystems, Foster City, CA), according to the manufacturer's instructions. The following primers and probes were used to measure RNA expression: for the full-length CTLA-4, forward primer: 59-GGACGCAGATTTATGTCATTGATC- 39 Expression of the genes coding for 36B4 and b-actin was used as endogenous control. CTLA-4, 36B4, and b-actin primers and probes were designed using Primer Express (Applied Biosystems).…”

Section: Reverse Transcription Followed By Quantitative Pcrmentioning

confidence: 99%

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Variation in the Cd3ζ (Cd247) Gene Correlates with Altered T Cell Activation and Is Associated with Autoimmune Diabetes

Lundholm

Mayans

Motta

et al. 2010

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Section: Reverse Transcription Followed By Quantitative Pcrmentioning

confidence: 99%

Variation in the Cd3ζ (Cd247) Gene Correlates with Altered T Cell Activation and Is Associated with Autoimmune Diabetes

Lundholm

Mayans

Motta

et al. 2010

The Journal of Immunology

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“…On Chr 11, Tucker has identified D11Mit207 (29 cm) as a weak marker associated with serum gp70 [24]. Using BXD RI lines of mice, T-cell proliferative unresponsiveness in NOD mice was mapped to a region on Chr 11 (49 cm) [25]. These results suggest that both Chrs 7 and 11 contain genetic loci that predisposes to autoimmune disease and dysregulation of BM stem cell development [26].…”

Section: Quantitative Trait Loci (Qtls) Affecting the Haematopoietic mentioning

confidence: 99%

Genetic Dissection of Age‐Related Changes of Immune Function in Mice

et al. 2001

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Understanding of the genetic basis of normal and abnormal development of the immune response is an enormous undertaking. The immune response, at the most minimal level, involves interactions of antigen presenting cells (APCs), T and B cells. Each of these cells produce cell surface and soluble factors (cytokines) that affect both autocrine and paracrine functions. A second level of complexity needs to consider the development of the macrophage/monocyte lineage as well as the production of the common lymphoid precursor which undergoes distinct maturation steps in the thymus and periphery to form mature T cells as well as in BM (BM) and lymphoid organs to form mature B cells. A third level of complexity involves the immune response to infectious agents including viruses and also the response to tumour antigens. In addition, there are imbalances that predispose to decreased responses (immunodeficiencies) or increased responses (autoimmunity). A fourth level of complexity involves attempts to understand the differences in the immune response that occurs at a very young age, in adults, and at a very old age. This review will focus on the use of C57BL/6 J X DBA/2 J (BXD) recombinant inbred (RI) strains of mice to map genetic loci associated with the production of lymphoid precursors in the BM, development of T cells in the thymus, and T-cell responses to stimulation in the peripheral lymphoid organs in adult and in aged mice. Strategies to improve the power and precision in which complex traits such as the age-related immune response can be mapped is limited with the current set of 35 strains of BXD mice. Strategies to increase these strains by generating recombinant intercross (RIX) strains of mice are being developed to enable this large set of lines to detect quantitative trait loci (QTLs) with a much higher consistency and statistical power. More importantly, the resolution with which these QTLs can be mapped would be greatly improved and, in many cases, adequate to carry out direct identification of candidate genes. It is likely that, given the complexity of the immune system development, the number of cells involved in an immune response, and especially the changes in the immune system with ageing, mapping hundreds of genes will be required to fully understand age-related changes in the immune response. This review outlines ongoing and future strategies that will enable the mapping and identification of these genes.

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“…Mononuclear cell infiltration of pancreatic islets and the progressive Th1 cell-mediated destruction of insulin-producing ␤ cells herald the onset of autoimmune type I diabetes. Previously, we found that the genetic control of NOD T cell proliferative hyporesponsiveness to engagement of the TCR is linked to a central region on chromosome 11 that includes the CC chemokine gene family and the Idd4 diabetes susceptibility locus (15). We also found that IL-4 treatment and CD28 costimulation prevent Th1-mediated destructive insulitis and type I diabetes in NOD mice by potentiation of regulatory Th2 cell function (16 -18).…”

mentioning

confidence: 89%

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

Cameron

Arreaza

Grattan

et al. 2000

The Journal of Immunology

133

107

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We investigated the biological role of CC chemokines in the Th1-mediated pathogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1α (MIP-1α):MIP-1β in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1α:MIP-1β ratio was observed in nonobese diabetes-resistant (NOR) mice. IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1β and monocyte chemotactic protein-1 (MCP-1): MIP-1α in the pancreas. Furthermore, NOD.MIP-1α−/− mice exhibited reduced destructive insulitis and were protected from diabetes. Neutralization of MIP-1α with specific Abs following transfer of diabetogenic T cells delayed the onset of diabetes in NOD.Scid recipients. These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1α, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes.

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Genetic Linkage of Thymic T-Cell Proliferative Unresponsiveness to Mouse Chromosome 11 in NOD Mice: A Possible Role for Chemokine Genes

Cited by 20 publications

References 24 publications

Variation in the Cd3ζ (Cd247) Gene Correlates with Altered T Cell Activation and Is Associated with Autoimmune Diabetes

Variation in the Cd3ζ (Cd247) Gene Correlates with Altered T Cell Activation and Is Associated with Autoimmune Diabetes

Genetic Dissection of Age‐Related Changes of Immune Function in Mice

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

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