Regula Mueller

TGF-β1 Alters APC Preference, Polarizing Islet Antigen Responses toward a Th2 Phenotype

TGF-beta1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-beta1 mice relied on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antigen, whereas T cells from ins-TGF-beta1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4 antibody, islet antigen-specific IFNGamma-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This suggests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-beta1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.

Flow Cytometric Measurement of ABO Antibodies in ABO-Incompatible Living Donor Kidney Transplantation

Due to different detection methods, a comparison of anti-A/B antibody (Ab) levels among transplantation centers after living donor ABO-incompatible kidney transplantation is problematic. In the present study, anti-A/B Ab levels were determined prior to, and after, blood group A-to-O kidney transplantation using a recently established semiquantitative flow cytometry-based method, ABO fluorescence-activated cell sorting (ABO-FACS), and compared with standard agglutination titers and indirect antiglobulin testing. Pretransplant agglutination titers were reduced from 1:64 to 1:4, by a total of 14 Glycosorb A column immunoadsorptions (IADSs). Compared with the agglutination titers, antidonor immunoglobulin (Ig) M ABO-FACS mean fluorescence intensity ratios (MFIRs) decreased faster and remained low. No difference was observed using donor type or third-party A red blood cells (RBCs) for the ABO-FACS. Glycosorb A columns were not specific, also reducing anti-B and antiporcine IgM levels, which was confirmed by detecting anti-A/B and antiporcine Abs in the column eluates. In conclusion, analysis of pre- and posttransplant Abs from ABO-incompatible kidney transplant recipients by ABO-FACS allows a better understanding of Ab kinetics, which may improve the design of future IADS protocols.

Transgenic/knockout mice — tools to study autoimmunity

Transgenic and knockout mice have been valuable tools for clarifying the roles of individual cell types and effector molecules in the pathogenesis of autoimmunity. During the past year, new strains have been added to the large array of transgenic mice, with broad or tissue-specific expression of transgene products. These laboratory models, as well as knockout mice lacking genes for a particular molecule, have greatly enhanced our understanding of autoimmune disease.

Interleukin-4 secretion by the allograft fails to affect the allograft-specific interleukin-4 response in vitro.

BACKGROUND The role of the cytokine, interleukin (IL)-4, in allograft rejection and protection is not clear. We have previously shown that IL-4 transgenically expressed in a pancreas allograft does not protect the allograft from rejection. Here, we analyze the effect of the transgenically expressed IL-4 on the cytokine profile of the allograft-specific immune response. METHODS C57BL/6SCID mice were infused with small numbers of spleen cells from C57BL/6 donors. The former received pancreas grafts from 1- to 2-day-old BALB/c donors which did or did not transgenically express IL-4 in the graft. Three weeks after the cell infusion, the spleens were removed and the splenocytes were restimulated in vitro with BALB/c APC, and third party BALB.K APC. IL-2 and IL-4 levels in the culture supernatants were measured. RESULTS The presence of a pancreatic allograft induced an increase in the levels of both IL-2 and IL-4 in culture supernatants from splenocytes of mice receiving grafts compared with mice not receiving grafts. The presence of IL-4 transgenically expressed in the pancreas allograft had no effect on the in vitro cytokine profile. CONCLUSIONS from these results we conclude that the failure of transgenically expressed IL-4 to protect the allograft was not associated with up-regulation of a graft antigen-specific IL-4 response.