ovalbumin and Glycosuria

NOD mice have a relative deficiency of CD4+CD25+ regulatory T cells that could result in an inability to maintain peripheral tolerance. The aim of this study was to induce the generation of CD4+CD25+ regulatory T cells in response to autoantigens to prevent type 1 diabetes (T1D). We found that immunization of NOD mice with insulin B-chain peptide B:9-23 followed by 72 h in vitro culture with B:9-23 peptide induces generation of CD4+CD25+ regulatory T cells. Route of immunization has a critical role in the generation of these cells. Non-autoimmune mice BALB/c, C57BL/6 and NOR did not show up regulation of CD4+CD25+ regulatory T cells. These cells secreted large amounts of TGF-beta and TNF-alpha with little or no IFN-gamma and IL-10. Adoptive transfer of these CD4+CD25+ regulatory T cells into NOD-SCID mice completely prevented the adoptive transfer of disease by diabetogenic T cells. Although, non-self antigenic OVA (323-339) peptide immunization and in vitro culture with OVA (323-339) peptide does result in up regulation of CD4+CD25+ T cells, these cells did not prevent transfer of diabetes. Our study for the first time identified the generation of antigen-specific CD4+CD25+ regulatory T cells specifically in response to immunization with B:9-23 peptide in NOD mice that are capable of blocking adoptive transfer of diabetes. Our results suggest the possibility of using autoantigens to induce antigen-specific regulatory T cells to prevent and regulate autoimmune diabetes.

Topics: Adoptive Transfer; Animals; Antibodies, Monoclonal; Antigen Presentation; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD3 Complex; CD4 Antigens; Coculture Techniques; Diabetes Mellitus, Type 1; Drug Administration Routes; Female; Glycosuria; Immune Tolerance; Insulin; Interferon-gamma; Interleukin-10; Islets of Langerhans; L-Selectin; Lectins, C-Type; Leukocyte Common Antigens; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Ovalbumin; Peptide Fragments; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptors, Interleukin-2; Spleen; T-Lymphocytes; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vaccination

The kidney tubulointerstitium has been reported to be protected from T-cell--mediated damage by sequestration from the T-cell compartment. We examined the ability of autoreactive T cells to infiltrate the kidney in a transgenic mouse model.. RIP-mOVA transgenic mice express the model autoantigen, membrane-bound ovalbumin (mOVA), in kidney proximal tubular cells and pancreatic beta cells. OVA-specific CD8(+) T cells (OT-I cells) were transferred into these recipient mice and their immune response against pancreas and kidney tissue was compared.. When OVA-specific CD8(+) T cells (OT-I cells) were injected into RIP-mOVA mice, they were activated in the renal and pancreatic lymph nodes by cross-presentation. These in vivo-activated OT-I cells caused the destruction of pancreatic islets leading to autoimmune diabetes, but did not infiltrate the kidney. Neither CD95--CD95 ligand interactions, which have been proposed to induce apoptosis in T cells infiltrating immunologically privileged sites, nor CD30 signaling was responsible for the lack of kidney infiltration. When OT-I cells were activated in vitro prior to injection, they could infiltrate the kidney and caused acute renal failure when injected in high numbers.. A mechanism distinct from previously described organ-specific protective mechanisms such as sequestration of antigen or CD95-mediated immunoprivilege contributes to the protection of the kidney tubulointerstitium from infiltration by autoreactive CD8(+) T cell.

Topics: Animals; Basement Membrane; CD8-Positive T-Lymphocytes; Diabetic Nephropathies; fas Receptor; Glycosuria; Homeodomain Proteins; Kidney Tubules, Proximal; Mice; Mice, Knockout; Nephritis, Interstitial; Ovalbumin; Receptors, Antigen, T-Cell; Signal Transduction