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The nonobese diabetic (NOD) mouse strain serves as a genomic standard for assessing how allelic variation for insulin-dependent diabetes ( Idd) loci affects the development of autoimmune diabetes. We previously demonstrated that C57BL/6 (B6) mice harbor a more diabetogenic allele than NOD mice for the Idd14 locus when introduced onto the NOD genetic background. New congenic NOD mouse strains, harboring smaller B6-derived intervals on chromosome 13, now localize Idd14 to an ~18-Mb interval and reveal a new locus, Idd31. Notably, the B6 allele for Idd31 confers protection against diabetes, but only in the absence of the diabetogenic B6 allele for Idd14, indicating genetic epistasis between these two loci. Moreover, congenic mice that are more susceptible to diabetes are more resistant to Listeria monocytogenes infection. This result co-localizes Idd14 and Listr2, a resistance locus for listeriosis, to the same genomic interval and indicates that congenic NOD mice may also be useful for localizing resistance loci for infectious disease. [ABSTRACT FROM AUTHOR]

Memory T cells exert antigen-independent effector functions, but how these responses are regulated is unclear. We discovered an in vivo link between flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells (DCs) and host protective interferon-? (IFN-?) secretion by noncognate memory CD8+ T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8?+ DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1?, only IL-18 was required for IFN-? production by memory CD8+ T cells. Conversely, only the release of IL-1?, but not IL-18, depended on priming signals mediated by Toll-like receptors. These findings provide a comprehensive mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity. [ABSTRACT FROM AUTHOR]

The mucosal secretory immune system provides an important primary defence against disease, as studies of humans with mucosal humoral immunodeficiencies suggest that the absence of secretory immunoglobulin A leads to an increase in mucosal infections. However, the infection risks posed do not seem to provide the evolutionary drive to retain constitutive secretion of often 'hard won' protein, suggesting that secretory antibodies may have some other important function (or functions). This Review examines the evidence that secretory antibodies provide an important defence against infection in specific animal models and explores complementary explanations for the evolution of the secretory immune system. [ABSTRACT FROM AUTHOR]

The most common models of CD4 T-cell deficiency are mice exogenously injected with anti-CD4 antibody (Ab), CD4 knockout (CD4−/−) and major histocompatibility complex (MHC) class II knockout (class II−/−) mice. We recently described the anti-CD4 Ab transgenic mouse (GK) as an improved CD4 cell-deficient model. This review compares this new GK mouse model with the widely available class II−/− and CD4−/− mice, when exposed to complex antigens (foreign grafts and during bacterial or viral infection). We highlight here the cytometric and functional differences (including Ab isotype, viral or bacterial clearance, and graft survival) among these CD4 cell-deficient models. For example, whereas grafts are generally rejected in class II−/− and CD4−/− mice as quickly as in wild-type mice, they survive longer in GK mice. Also, CD4−/− mice produce IgG against both simple model and complex antigens, but class II−/− and GK mice produce small amounts of IgG2a against complex antigens but not simple model antigens. These differences harbinger the caveats in the use of these various mice. [ABSTRACT FROM AUTHOR]