Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase

The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression

Testing the Water–Energy Theory on American Palms (Arecaceae) Using Geographically Weighted Regression

Water and energy have emerged as the best contemporary environmental correlates of broad-scale species richness patterns. A corollary hypothesis of water–energy dynamics theory is that the influence of water decreases and the influence of energy increases with absolute latitude. We report the first use of geographically weighted regression for testing this hypothesis on a continuous species richness gradient that is entirely located within the tropics and subtropics. The dataset was divided into northern and southern hemispheric portions to test whether predictor shifts are more pronounced in the less oceanic northern hemisphere. American palms (Arecaceae, n = 547 spp.), whose species richness and distributions are known to respond strongly to water and energy, were used as a model group. The ability of water and energy to explain palm species richness was quantified locally at different spatial scales and regressed on latitude. Clear latitudinal trends in agreement with water–energy dynamics theory were found, but the results did not differ qualitatively between hemispheres. Strong inherent spatial autocorrelation in local modeling results and collinearity of water and energy variables were identified as important methodological challenges. We overcame these problems by using simultaneous autoregressive models and variation partitioning. Our results show that the ability of water and energy to explain species richness changes not only across large climatic gradients spanning tropical to temperate or arctic zones but also within megathermal climates, at least for strictly tropical taxa such as palms. This finding suggests that the predictor shifts are related to gradual latitudinal changes in ambient energy (related to solar flux input) rather than to abrupt transitions at specific latitudes, such as the occurrence of frost