Genetic dissection of V alpha 14J alpha 18 natural T cell number and function in autoimmune-prone mice.

Matsuki N, Stanic AK, Embers ME, Van Kaer L, Morel L, Joyce S
J Immunol. 2003 170 (11): 5429-37

PMID: 12759418 · DOI:10.4049/jimmunol.170.11.5429

Nonobese diabetic (NOD) mice, a model for type I diabetes (TID), have reduced numbers of invariant V alpha 14J alpha 18 TCR alpha-chain-positive natural T (iNKT) cells that do not release IL-4 in response to in vivo activation through their Ag receptor. The deficit in iNKT cell number and function is implicated in immune dysregulation and the etiology of TID. Therefore, we reasoned that the genetic determinant(s) that controls iNKT cell number and function might lie within Idd (insulin-dependent diabetes susceptibility locus) regions, which are known to contain TID resistance or susceptibility genes. A systematic analysis of iNKT cell number and function in Idd congenic mice revealed that neither iNKT cell number nor their inability to rapidly secrete IL-4 in response to acute in vivo activation by Ag underlies the mechanism of protection from diabetes in Idd congenic mice. Moreover, the regulation of iNKT cell number and function appears to be under the control of several genes. The most notable of these map to the Idd4, Idd5, Idd9.1, and Idd13 regions of the mouse genome. Together these findings provide a clue to the genetic mechanism(s) underlying iNKT cell deficiency in NOD mice.

MeSH Terms (24)

Animals Antigens Cytokines Diabetes Mellitus, Type 1 Galactosylceramides Genetic Markers Genetic Predisposition to Disease Immunity, Innate Injections, Intravenous Interferon-gamma Interleukin-4 Killer Cells, Natural Lymphocyte Activation Lymphocyte Count Mice Mice, Congenic Mice, Inbred C57BL Mice, Inbred NOD Mice, Inbred NZB Mice, Mutant Strains Receptors, Antigen, T-Cell, alpha-beta T-Lymphocyte Subsets Transcriptional Activation Up-Regulation

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