Unfortunately, HLA class II expression did not enable the PBMC-DQ8 transplanted DQ8 mice to develop a humoral immune response, which requires the collaboration of T with B cells (data not shown). Because B cells

did not survive in this adoptive PBMC model, this is expected. Also, it limits the usefulness of this model for testing purposes, such as testing vaccines for which a humoral immune response has been shown to be essential to mediate protection. If a regimen can be established allowing for preservation of the B cell subset, it will be an interesting retest for this immune function. Currently, however, even though tests relying upon humoral responses are not possible, this does not mean that CD4+ T cell responses are not occurring. Thus, direct assays for CD4+ T cell function,

such as lymphokine production in response to test antigens, could well be possible. It see more could also allow testing of whether a donor was primed to the given antigen, and thus became immune, during the testing of new therapeutic vaccines relying upon a cellular immune reaction. This mouse model could provide a personalized animal model to test vaccine efficacies in vivo. Potentially, the transfer of PBMCs of vaccinated people followed by a challenge infection in the mouse could provide indications of the effectiveness of cell-mediated vaccines. In this respect, the mouse model described in this study could be of considerable value for human immunodeficiency virus (HIV) vaccine testing, PS-341 purchase as HIV has a very limited host tropism and replicates almost Ribonucleotide reductase exclusively in human CD4+ T cells. Finally, NRG Aβ–/–DQ8tg mice are a useful model to test experimentally for modalities reducing GVHD in partially allogeneic or minor histocompatibility disparate

settings. Similar to recently published data, the engraftment could be limited to CD4+ cells to focus upon the contribution to GVHD by these cells [33]. A further refinement would be to cross NRG Aβ–/– DQ8tg with MHC class I knock-out mice. In these, the CD8+-mediated component of GVHD would be eliminated, and this could make the mice suitable even for long-term studies. Overall, this newly generated mouse strain shows prolonged survival and delayed onset of GVHD after transplantation with haplotype-matched human PBMCs. Thus, it is a superior model with which to study GVHD, and it could be valuable to investigate CD4+ T cell responses for certain human vaccines and pathogens. We thank Heike Baumann, Christine von Rhein and Sophie Wald for excellent technical assistance and Kay-Martin Hanschmann for help with statistical analysis. This work was funded in part by the German Federal Ministry of Health. The authors have no disclosures in relation to the article.