Tissue inhibitor of metalloproteinase-2 inhibits T-cell infiltration and preserves pancreatic β-cell function in an in vitro type 1 diabetes mellitus model

Woods, Chris C.; Sundar, Krishnan; Tessler, C.; Lebsack, Ty W.; Grainger, Lora Ann; Nielsen, Alma; Bleich, David; DeLuca, Dominick

doi:10.1016/j.jaut.2006.04.004

Cited by 16 publications

(17 citation statements)

References 32 publications

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“…Our study showed that although LEW and WKY rats were immuno-compatible and mounted a similar immune response to the nephritogenic T cell epitope pCol (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), WKY rats were highly GN-susceptible while LEW rats were GN-resistant. In fact, resistance to autoimmune disease induction is common in animal models for autoimmune diseases, including other anti-GBM GN models (6,7,(19)(20)(21).…”

Section: Discussionmentioning

confidence: 72%

“…This is not surprising because B cell epitope spreading would never occur without glomerular damage (16). In conclusion, LEW rats were resistant to GN induction despite having a MHC and T cell response to pCol (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) identical to that seen in WKY rats. These results suggest that anti-GBM GN susceptibility in WKY is not associated with MHC type, or Th type and specificity of T cell response.…”

Section: Lew Rats Are Resistant To Gn Inductionmentioning

confidence: 87%

“…In addition, local environment and innate immunity may also play very important role in pathogenesis. For example, inhibition of metalloproteinase inhibited T cell's attack on b-cell in a diabetes model (36,37) WKY rats are highly susceptible to several types of GN (6,7,38,39). Thus, discovery of a new mechanism in WKY may contribute to our understanding of mechanisms of glomerular injury in other types of GN as well.…”

Section: Discussionmentioning

confidence: 99%

“…Since the two strains have identical RT-1B, T cell lines generated from the immunized LEW rats responded well to APC from WKY and vice versa (Fig.2B). Second, the T cell lines from the two strains were tested for their specificity in recognition of pCol (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). The T cells were stimulated with a set of pCol (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) peptides with single substitution (Fig.…”

Section: Lew and Wky Rats Mount Similar Immune Response To Nephritogementioning

confidence: 99%

“…However, the nature of this leukocyte population was not determined in this study. Second, we examined expression of inflammatory molecules in the glomeruli after immunization with pCol (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) in both LEW and WKY at day 20 and day 30 (Fig. 6).…”

Section: Lew Develops T Cell-mediated Glomerular Inflammation Similarmentioning

confidence: 99%

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Spontaneous recovery from early glomerular inflammation is associated with resistance to anti-GBM glomerulonephritis: tolerance and autoimmune tissue injury

Robertson

Arends

et al. 2008

Journal of Autoimmunity

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Different susceptibility to anti-GBM glomerulonephritis (GN) among animal strains has been reported. Using our rat model for T cell-mediated anti-GBM GN, this study initiated an investigation on the mechanism related with GN-susceptibility. Anti-GBM GN was induced either though immunization with the nephritogenic T cell epitope pCol(28-40) from Col4α3NC1 or through the transfer of specific T cells. WKY rats were highly susceptible to GN while immuno-compatible LEW rats were GN-resistant. GN-resistance in LEW rats was not associated immune response to pCol (28-40). First, both strains mounted a Th1 T cell response to pCol(28-40) with identical specificities; transfer of T cells from LEW to WKY rats induced glomerular injury. Second, co-transfer of antibody from WKY to LEW failed to induce GN. Time-course studies revealed that LEW rats did develop T cell-mediated inflammation in glomeruli at early stages similar to WKY rats, as evidenced by histopathology, proteinuria, CD4 + T cell infiltration in glomeruli, and glomerular expression of inflammatory molecules. However, glomerular inflammation in LEW rats was transient followed by a full recovery. Thus, GN-resistance in LEW rats was due to its ability to contain early T cell-mediated autoimmune glomerular damage. Our model may reveal a potential tolerance mechanism after autoimmune tissue damage has been initiated.

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