Murine CD83-positive T cells mediate suppressor functions in vitro and in vivo.

The CD83 molecule (CD83) is a well-known surface marker present on mature dendritic cells (mDC). In this study, we show that CD83 is also expressed on a subset of T cells which mediate regulatory T cell (Treg)-like suppressor functions in vitro and in vivo. Treg-associated molecules including CD25, cytotoxic T lymphocyte antigen-4 (CTLA-4), glucocorticoid-induced TNFR family-related gene (GITR), Helios and neuropilin-1 (NRP-1) as well as forkhead box protein 3 (FOXP3) were specifically expressed by these CD83(+) T cells. In contrast, CD83(-) T cells showed a naive T cell phenotype with effector T cell properties upon activation. Noteworthy, CD83(-) T cells were not able to upregulate CD83 despite activation. Furthermore, CD83(+) T cells suppressed the proliferation and inflammatory cytokine release of CD83(-) T cells in vitro. Strikingly, stimulated CD83(+) T cells released soluble CD83 (sCD83), which has been reported to possess immunosuppressive properties. In vivo, using the murine transfer colitis model we could show that CD83(+) T cells were able to suppress colitis symptoms while CD83(-) T cells possessed effector functions. In addition, this CD83 expression is also conserved on expanded human Treg. Thus, from these studies we conclude that CD83(+) T cells share important features with regulatory T cells, identifying CD83 as a novel lineage marker to discriminate between different T cell populations.

B cells in classical Hodgkin lymphoma are important actors rather than bystanders in the local immune reaction.

Recent studies, largely focusing on cellular immunity, have demonstrated that the composition of the abundant inflammatory background of Hodgkin lymphoma may affect outcome. This investigation aimed to characterize the potential role of infiltrating B cells and follicular dendritic cell networks in classical Hodgkin lymphoma (cHL) to better assess the role of components of humoral immunity. One hundred two cHL biopsies were investigated by immunohistochemistry with antibodies specific for CD20, CD138, activation-induced cytidine deaminase, and CD21 to characterize B cell distribution and follicular structures. To further subclassify B cells, analyses of tissue microarrays were performed investigating the expression of Mum1, Bcl6, IgD, IgG, IgG4, IgM, T-bet, CD38, CD5, and CD10. For evaluation a computer assisted quantification method was compared with a scoring system. Survival analysis and correlation analysis were performed. The B cell infiltrate was dominated by CD20+ B cells, followed by plasma cells, whereas only few AID+ cells were observed. High numbers of CD21+ follicular dendritic cell networks, CD20+ B cells, IgM+ cells, CD20+ aggregates, and Bcl6+ cells were associated with a better outcome of cHL patients, whereas Pax5+/CD38+ cells had an adverse prognostic impact. Other parameters showed no influence on survival. Our findings suggest that a complex network of B cells is present in the microenvironment of cHL and that B cells might actively contribute to a local anti- as well as pro-tumoral immune response. This indicates that the network of B cells in tumors is probably just as diverse as the T cellular infiltrate and probably functionally as heterogenous.

Murine whole-organ immune cell populations revealed by multi-epitope-ligand cartography.

Multi-epitope-ligand cartography (MELC) is an innovative high-throughput fluorescence microscopy-based method. A tissue section is analyzed through a repeated cycling of (1) incubation with a fluorophore-labeled antibody, (2) fluorescence imaging, and (3) soft bleaching. This method allows staining of the same tissue section with up to 100 fluorescent markers and to analyze their toponomic expression using further image processing and pixel-precise overlay of the corresponding images. In this study, we adapted this method to identify a large panel of murine leukocyte subpopulations in a whole frozen section of a peripheral lymph node. Using the resulting antibody library, we examined non-inflamed versus inflamed tissues of brain and spinal cord in the experimental autoimmune encephalomyelitis (EAE) model. The presence and activity of specific leukocyte subpopulations (different T cell subpopulations, dendritic cells, macrophages, etc.) could be assessed and the cellular localizations and the corresponding activation status in situ were investigated. The results were then correlated with quantitative RT-PCR.

Growth of transgenic RAF-induced lung adenomas is increased in mice with a disrupted PPARbeta/delta gene.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors with essential functions in regulating lipid metabolism. Both the PPARbeta (also referred to as PPARdelta) and PPARgamma subtype have been reported to either attenuate or potentiate tumorigenesis in a number of different models of intestinal and skin carcinogenesis. In the present study, we have addressed the role of PPARbeta and PPARgamma in lung tumorigenesis in a transgenic mouse model of RAF-induced lung adenoma using two different strategies: i) crossing with PPARbeta null mice, and ii) chronic treatment with the PPARgamma agonist rosiglitazone. Histological examination revealed a significant enhancement of tumor growth in mice lacking one or both alleles of Pparb, but no significant effect in response to rosiglitazone. These observations indicate i) that RAF-induced lung tumorigenesis is attenuated in mice with a disrupted Pparb gene, and ii) that chronic PPARgamma activation does not affect lung adenoma growth. These results are relevant with respect to the clinical application of drugs modulating the activity of PPARbeta or PPARgamma.