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An NZW-derived interval on chromosome 7 moderates sialadenitis, but not insulitis in congenic nonobese diabetic mice

- Burt, Rachel, Watkins, Laura, Tan, Iris, Wang, Nancy, Quirk, Fiona, Mackin, Leanne, Morgan, Phillip, Zhang, Jian-Guo, Berzins, Stuart, Morahan, Grant, Brodnicki, Thomas

  • Authors: Burt, Rachel , Watkins, Laura , Tan, Iris , Wang, Nancy , Quirk, Fiona , Mackin, Leanne , Morgan, Phillip , Zhang, Jian-Guo , Berzins, Stuart , Morahan, Grant , Brodnicki, Thomas
  • Date: 2010
  • Type: Text , Journal article
  • Relation: Journal of Immunology Vol. 184, no. 2 (2010), p. 859-868
  • Full Text: false
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  • Description: Autoimmune lymphocytic infiltration of the salivary glands, termed sialadenitis, is a pathologic feature of Sjögren's syndrome (SjS) that is also prominent in nonobese diabetic (NOD) mice. Genetic factors regulate sialadenitis, and a previous (NOD x NZW)F2 study detected linkage to murine chromosome (Chr) 7. The locus, subsequently annotated as Ssial3, maps to the distal end of Chr7 and overlaps a region associated with type 1 diabetes susceptibility in NOD mice. To examine whether Ssial3 could contribute to both diseases, or was specific for SjS, we generated a congenic mouse strain that harbored an NZW-derived Chr7 interval on the NOD genetic background. This congenic strain exhibited reduced sialadenitis compared with NOD mice and confirmed Ssial3. This reduction, however, did not ameliorate saliva abnormalities associated with SjS-like disease in NOD mice, nor were congenic mice protected against insulitis (lymphocytic infiltration of the pancreatic islets) or diabetes onset. Thus, the Ssial3 locus appears to have a tissue-specific effect for which the NZW allele is unable to prevent other autoimmune traits in the NOD mouse. Anomalous increases for antinuclear Ab production and frequency of marginal-zone B cells were also identified in congenic mice, indicating that theNZW-derived Chr7 interval has a complex effect on the NOD immune system. Copyright © 2010 by The American Association of Immunologists, Inc.

Immune characterization of an individual with an exceptionally high natural killer T cell frequency and her immediate family

- Chan, Angela, Serwecinska, Liliana, Cochrane, Andrew, Harrison, Leonard, Godfrey, Dale, Berzins, Stuart

  • Authors: Chan, Angela , Serwecinska, Liliana , Cochrane, Andrew , Harrison, Leonard , Godfrey, Dale , Berzins, Stuart
  • Date: 2009
  • Type: Text , Journal article
  • Relation: Clinical and Experimental Immunology Vol. 156, no. 2 (May 2009 2009), p. 238-245
  • Full Text: false
  • Reviewed:
  • Description: Natural killer T cells (NKT) are a regulatory subset of T lymphocytes whose frequency in peripheral blood is highly variable within the human population. Lower than normal NKT frequencies are associated with increased predisposition to a number of diseases, including type 1 diabetes and some forms of cancer, raising the possibility that an increased frequency may be protective. However, there is little or no understanding of how high NKT frequencies arise or, most importantly, whether the potential exists to boost and maintain NKT levels for therapeutic advantage. Here, we provide a detailed functional and phenotypic characterization of the NKT compartment of a human donor with NKT levels approximately 50 times greater than normal, including an analysis of NKT in her immediate family members. The study focuses upon the characteristics of this donor and her family, but demonstrates more broadly that the size and flexibility of the NKT niche is far greater than envisioned previously. This has important implications for understanding how the human NKT compartment is regulated, and supports the concept that the human NKT compartment might be expanded successfully for therapeutic benefit.
  • Description: C1
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