Pentagonal PdX2 (X = S, Se) nanosheets with X vacancies as high-performance electrocatalysts for the hydrogen evolution reaction.

Two-dimensional transition metal dichalcogenides (TMDs) have emerged as promising catalysts for the hydrogen evolution reaction (HER). However, they typically require the engineering of additional actives sites (e.g. vacancies and dopants) and/or the application of large external strains to launch the HER on their basal planes. Herein, we investigate the HER proceeding on the experimentally available single-layer PdX2 (X = S, Se), a novel group of pentagonal TMDs with high amounts of intrinsic X vacancies, through density functional theory computations. Our results indicate that single-layer PdX2 nanosheets with low concentrations of X vacancies exhibit favorable hydrogen adsorption free energy (ΔGH*) values, which is desirable for facilitating the HER. Their HER performance can be greatly enhanced using small external strains, during which ΔGH* can reach the optimal value of 0 eV. Moreover, a kinetic analysis based on the explicit water model and charge extrapolation scheme demonstrates that the HER occurs on the PdX2 nanosheets according to the Volmer-Tafel mechanism with low energy barriers. This work highlights the realization of high HER activity on TMDs featuring unique structural characteristics.

Phase-Controlled Synthesis of Pd-Se Nanocrystals for Phase-Dependent Oxygen Reduction Catalysis.

Searching for highly efficient oxygen reduction reaction (ORR) electrocatalysts for fuel cell technology, in which the crystal structure plays a powerful role in regulating the electrocatalysis, is urgent yet challenging. Herein, we have explored the active and stable Pd-Se alloy electrocatalysts with controlled phase toward alkaline ORR. The phase-controlled Pd-Se nanoparticles (NPs) show interesting phase-dependent electrocatalytic performance, in which the Pd17Se15 NPs/C exhibits much better ORR performance than its counterpart, Pd7Se4 NPs/C, and the commercial Pd/C and Pt/C. Based on the detailed analysis, Pd in Pd17Se15 possesses more Se atom coordination and a higher valence state, thus providing a stronger capacity for the absorption of oxygenated species. DFT further reveals more charge transfer from the Pd17Se15 surface to the *OOH intermediate, which is the reason for the activity enhancement.

In-depth phenotypic characterization of reticulocyte maturation using mass cytometry.

Progress towards an in-depth understanding of the final steps of the erythroid lineage development is paramount for many hematological diseases. We have characterized the final stages of reticulocyte maturation from bone marrow to peripheral blood using for the first time single-cell Mass Cytometry (CyTOF). We were able to measure the expression of 31 surface markers within a single red blood cell (RBC). We demonstrate the validity of CyTOF for RBC phenotyping by confirming the progressive reduction of transferrin receptor 1 (CD71) during reticulocyte maturation to mature RBC. We highlight the high-dimensional nature of mass cytometry data by correlating the expression of multiple proteins on individual RBCs. We further describe a more drastic reduction pattern for a component of the alpha4/beta1 integrin CD49d at the very early steps of reticulocyte maturation in bone marrow and directly linked with the mitochondria remnants clearance pattern. The enhanced and accurate RBC phenotyping potential of CyTOF described herein could be beneficial to decipher RBC preferences, as well as still not well understood receptor-ligand interaction of some hemotropic parasites such as the malaria causing agent Plasmodium vivax.

Oxidative stress changes the effectiveness of artemisinin in Plasmodium falciparum.

Malaria parasites have adaptive mechanisms to modulate their intracellular redox status to tolerate the enhanced oxidizing effects created by malaria fever, hemoglobinopathies and other stress conditions, including antimalaria drugs. Emerging artemisinin (ART) resistance in Plasmodium falciparum is a complex phenotype linked to the parasite's tolerance of the activated drug's oxidative damage along with changes in vesicular transport, lipid metabolism, DNA repair, and exported proteins. In an earlier study, we discovered that many of these metabolic processes are induced in P. falciparum to respond to the oxidative damage caused by artemisinin, which exhibited a highly significant overlap with the parasite's adaptive response mechanisms to survive febrile temperatures. In addition, there was a significant overlap with the parasite's survival responses to oxidative stress. In this study, we investigated these relationships further using an in vitro model to evaluate if oxidative stress and heat-shock conditions could alter the parasite's response to artemisinin. The results revealed that compared to ideal culture conditions, the antimalarial efficacy of artemisinin was significantly reduced in parasites growing in intraerythrocytic oxidative stress but not in heat-shock condition. In contrast, heat shock significantly reduced the efficacy of lumefantrine that is an important ART combination therapy partner drug. We propose that prolonged exposure to intraerythrocytic microenvironmental oxidative stress, as would occur in endemic regions with high prevalence for sickle trait and other hemoglobinopathies, can predispose malaria parasites to develop tolerance to the oxidative damage caused by antimalarial drugs like artemisinin. IMPORTANCE: Emerging resistance to the frontline antimalarial drug artemisinin represents a significant threat to worldwide malaria control and elimination. The patterns of parasite changes associated with emerging resistance represent a complex array of metabolic processes evident in various genetic mutations and altered transcription profiles. Genetic factors identified in regulating P. falciparum sensitivity to artemisinin overlap with the parasite's responses to malarial fever, sickle trait, and other types of oxidative stresses, suggesting conserved inducible survival responses. In this study we show that intraerythrocytic stress conditions, oxidative stress and heat shock, can significantly decrease the sensitivity of the parasite to artemisinin and lumefantrine, respectively. These results indicate that an intraerythrocytic oxidative stress microenvironment and heat-shock condition can alter antimalarial drug efficacy. Evaluating efficacy of antimalarial drugs under ideal in vitro culture conditions may not accurately predict drug efficacy in all malaria patients.

Do the policy burdens of state-owned enterprises affect the efficiency of resource allocation of tax incentives?

State-owned enterprises (SOEs) bear a significant policy burden in promoting economic development and enjoy preferential government resources such as tax breaks. This study investigates the effect of the policy burden of China's SOEs on tax incentive resources and allocation efficiency using ordinary least squares regressions for state-owned listed companies from 2007 to 2021. This study found that the heavier the policy burden borne by the SOEs, the more tax incentives they receive. Moreover, SOEs become more likely to invest inefficiently after receiving tax incentives. These negative effects are more significant for local SOEs, those in poor business environments, and those with low information transparency. This study not only expands the research framework of the resource allocation efficiency of tax incentives but also provides direct empirical evidence to reduce the policy burden of SOEs. Therefore, our findings can be used to promote SOE reforms.

Environmental protection tax and green innovation.

How environmental taxes affect green innovation in businesses is closely related to enterprise sustainable development and green economic development. This study uses the data of non-financial listed companies from 2010 to 2020 in China, and adopts the difference-in-difference method to examine the effect of the environmental protection tax (EPT) on corporate green innovation in China. Results show that EPT reform has a significantly negative effect on corporate green innovation, and the robustness test supports this result. EPT has a larger inhibitory effect on non-state-owned enterprises' green innovation than state-owned enterprises. This inhibiting effect is particularly prominent in companies situated in northern and low-marketization regions. Further analysis shows that EPT affects enterprises' green innovation by reducing the cash flow and financing of enterprises. This study provides an empirical basis for the implementation of the EPT policy.

Governance of non-state-owned shareholders and corporate capital structure decision: A mechanism test from the opportunistic behavior of management.

It is an important measure in the reform of state-owned enterprises to improve the efficiency of capital operation by introducing non-state-owned shareholders. This paper explores the impact of non-state shareholder governance on capital structure decision-making by using the data of 2008-2021 A-share state-owned listed companies from the perspective of the speed and deviation of capital structure adjustment. The results reveal that only non-state shareholding has no significant impact on the capital structure adjustment of a company. However, the appointment of senior management by non-state shareholders can speed up the capital structure adjustment and lower the degree of capital structure deviation. Moreover, when the capital structure goes down, the appointment of non-state-owned shareholders plays a larger role in accelerating the capital structure adjustment, which makes the deviation from the actual capital structure and the target capital structure smaller. Further research shows that the above relationship between non-state shareholder governance and the optimization and adjustment of the capital structure only exists in local SOEs and competitive SOEs. In addition, the path test found that non-state shareholder governance affects the dynamic adjustment of capital structure by reducing opportunism behavior of management rather than by financing constraints.

COVID-19 Related Early Google Search Behavior and Health Communication in the United States: Panel Data Analysis on Health Measures.

The COVID-19 outbreak at the end of December 2019 spread rapidly all around the world. The objective of this study is to investigate and understand the relationship between public health measures and the development of the pandemic through Google search behaviors in the United States. Our collected data includes Google search queries related to COVID-19 from 1 January to 4 April 2020. After using unit root tests (ADF test and PP test) to examine the stationary and a Hausman test to choose a random effect model, a panel data analysis is conducted to investigate the key query terms with the newly added cases. In addition, a full sample regression and two sub-sample regressions are proposed to explain: (1) The changes in COVID-19 cases number are partly related to search variables related to treatments and medical resources, such as ventilators, hospitals, and masks, which correlate positively with the number of new cases. In contrast, regarding public health measures, social distancing, lockdown, stay-at-home, and self-isolation measures were negatively associated with the number of new cases in the US. (2) In mild states, which ranked one to twenty by the average daily new cases from least to most in 50 states, the query terms about public health measures (quarantine, lockdown, and self-isolation) have a significant negative correlation with the number of new cases. However, only the query terms about lockdown and self-isolation are also negatively associated with the number of new cases in serious states (states ranking 31 to 50). Furthermore, public health measures taken by the government during the COVID-19 outbreak are closely related to the situation of controlling the pandemic.

Risk attitudes and household consumption behavior: Evidence from China.

Risk attitude is a vital component of public mental health. Thus, the public should be guided to fully comprehend risks to improve public mental health. Using panel data from China Household Finance Survey (CHFS) in 2017, this study examined the impact of risk attitudes on household consumption behavior by constructing a micro-econometric model. Results suggest that risk attitude can promote household consumption, with multiple robustness tests supporting this conclusion. In addition, after dividing the consumption types into subsistence consumption, development consumption, and enjoyment consumption, we show risk preference promotes all three types of consumption and has the greatest impact on enjoyment consumption. Concurrently, risk neutrality can promote household survival consumption, but its promotion effect is smaller than that of risk preference. Moreover, risk aversion has an inhibitory effect on total consumption behavior, but this inhibitory effect does not show heterogeneity for different consumption behaviors. Heterogeneity analysis found that for male households, risk attitude remains an important factor in consumption behavior. When men's risk attitude is more risk averse, it can promote more survival consumption, whereas women's risk attitude is more risk averse. With increasing age, risk attitude remains a crucial factor in the occurrence of consumer behavior. However, education level has no bearing on the effect of risk attitude on household consumption behavior. This research holds theoretical and practical significance for improving public mental health, optimizing residents' consumption structure, and achieving high-quality economic development.

Influencing factors of environmental efficiency of strategic emerging industries and their power cooperation mechanism design.

We investigate the influencing factors of environmental efficiency of strategic emerging industries (SEIs) and cooperative game mechanism design amongst diversified actors by using China's provincial panel data from 2004 to 2019. Firstly, we find that the following factors improve the environmental efficiency of SEIs: rationalisation of the industrial structure, proportion of the tertiary industry, government's ability to intervene in the economy and fairness and integrity of environmental law enforcement. Conversely, factors, such as intensity of ecological construction and environmental regulation, hamper the environmental efficiency of SEIs. Secondly, evolutionary game analysis indicates that the behavioural strategies of game decision-making subjects depend on the behavioural decisions of the relative actors, social supervision and government regulation, which work together in influencing the environmental efficiency of SEIs. {innovation, supervision} is the optimal equilibrium state of the game. Thirdly, simulation results show that in the absence of government regulation, foreign direct investment (FDI) slows down the speed of firms tending to the equilibrium state of green innovation. The potential gain and loss of social supervision on corporate behaviour is an important factor affecting government behaviour decision making. Governments prefer punishment tools in environmental regulation, therefore influencing noninnovative firms in SEIs. We contribute to prior works by unifying various policy tools into the same econometric model framework based on an evolutionary game model.

Does Financial Literacy Affect Household Financial Behavior? The Role of Limited Attention.

Financial literacy is essential for every individual concerned with public welfare and household portfolio choices. In this study, we investigate the impact of household financial literacy on individuals' financial behavior using the China Household Financial Survey Data (CHFS) of 2015 and 2017. The results show that financial knowledge has significant current, long-term, and dynamic effects on financial behavior. This finding suggests that financial literacy is an important factor in shaping and improving financial behavior. Second, financial literacy can improve residents' limited attention, and residents with high attention tend to have formal bank accounts, participate in the stock market, and engage in financial behaviors in situations such as risky financial markets. High attention also helps to improve residents' financial behavior. This relationship suggests that financial literacy positively impacts formal bank account holding, participation in financial markets, participation in commercial insurance, participation in pension plans, and credit card holdings through limited attention channels that facilitate access to specific financial information. In addition, heterogeneity analysis showed that the impact of financial literacy on financial behavior differs significantly between urban and rural households, between men and women, and between high and low education levels. The study provides valuable insights for policy implications to enhance financial literacy, such as carrying out financial training to improve residents' knowledge about financial aspects, which further helps to optimize household financial decision-making.

Variable immunogenicity of a vivax malaria blood-stage vaccine candidate.

Relapsing malaria caused by Plasmodium vivax is a neglected tropical disease and an important cause of malaria worldwide. Vaccines to prevent clinical disease and mosquito transmission of vivax malaria are needed to overcome the distinct challenges of this important public health problem. In this vaccine immunogenicity study in mice, we examined key variables of responses to a P. vivax Duffy binding protein vaccine, a leading candidate to prevent the disease-causing blood-stages. Significant sex-dependent differences were observed in B cell (CD80+) and T cell (CD8+) central memory subsets, resulting in significant differences in functional immunogenicity and durability of anti-DBP protective efficacy. These significant sex-dependent differences in inbred mice were in the CD73+CD80+ memory B cell, H2KhiCD38hi/lo, and effector memory subsets. This study highlights sex and immune genes as critical variables that can impact host responses to P. vivax antigens and must be taken into consideration when designing clinical vaccine studies.

The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.

The emergence and spread of Plasmodium falciparum parasites resistant to front-line antimalarial artemisinin-combination therapies (ACT) threatens to erase the considerable gains against the disease of the last decade. Here, we develop a large-scale phenotypic screening pipeline and use it to carry out a large-scale forward-genetic phenotype screen in P. falciparum to identify genes allowing parasites to survive febrile temperatures. Screening identifies more than 200 P. falciparum mutants with differential responses to increased temperature. These mutants are more likely to be sensitive to artemisinin derivatives as well as to heightened oxidative stress. Major processes critical for P. falciparum tolerance to febrile temperatures and artemisinin include highly essential, conserved pathways associated with protein-folding, heat shock and proteasome-mediated degradation, and unexpectedly, isoprenoid biosynthesis, which originated from the ancestral genome of the parasite's algal endosymbiont-derived plastid, the apicoplast. Apicoplast-targeted genes in general are upregulated in response to heat shock, as are other Plasmodium genes with orthologs in plant and algal genomes. Plasmodium falciparum parasites appear to exploit their innate febrile-response mechanisms to mediate resistance to artemisinin. Both responses depend on endosymbiont-derived genes in the parasite's genome, suggesting a link to the evolutionary origins of Plasmodium parasites in free-living ancestors.

Antigen specificity acquisition of adoptive CD4+ regulatory T cells via acquired peptide-MHC class I complexes.

The Ag-specific CD4(+) regulatory T (Tr) cells play an important role in immune suppression in autoimmune diseases and antitumor immunity. However, the molecular mechanism for Ag-specificity acquisition of adoptive CD4(+) Tr cells is unclear. In this study, we generated IL-10- and IFN-gamma-expressing type 1 CD4(+) Tr (Tr1) cells by stimulation of transgenic OT II mouse-derived naive CD4(+) T cells with IL-10-expressing adenovirus (AdV(IL-10))-transfected and OVA-pulsed dendritic cells (DC(OVA/IL-10)). We demonstrated that both in vitro and in vivo DC(OVA/IL-10)-stimulated CD4(+) Tr1 cells acquired OVA peptide MHC class (pMHC) I which targets CD4(+) Tr1 cells suppressive effect via an IL-10-mediated mechanism onto CD8(+) T cells, leading to an enhanced suppression of DC(OVA)-induced CD8(+) T cell responses and antitumor immunity against OVA-expressing murine B16 melanoma cells by approximately 700% relative to analogous CD4(+) Tr1 cells without acquired pMHC I. Interestingly, the nonspecific CD4(+)25(+) Tr cells can also become OVA Ag specific and more immunosuppressive in inhibition of OVA-specific CD8(+) T cell responses and antitumor immunity after uptake of DC(OVA)-released exosomal pMHC I complexes. Taken together, the Ag-specificity acquisition of CD4(+) Tr cells via acquiring DC's pMHC I may be an important mean in augmenting CD4(+) Tr cell suppression.

Defect of CD8+ memory T cells developed in absence of IL-12 priming for secondary expansion.

IL-12 priming plays an important role in stimulation of CD8+ effector T cells and development of CD8+ memory T (Tm) cells. However, the functional alteration of CD8+ Tm cells developed in the absence of IL-12 priming is elusive. In this study, we investigated the capacity of secondary expansion of CD8+ Tm cells developed from transgenic OT I CD8+ T cells. The latter cells were in vitro and in vivo stimulated by ovalbumin (OVA)-pulsed dendritic cells [DCOVA and (IL-12-/-)DCOVA] derived from wild-type C57BL/6 and IL-12 gene knockout mice, respectively. We demonstrated that IL-12 priming is important not only in CD8+ T cell clonal expansion, but also in generation of CD8+ Tm cells with the capacity of secondary expansion upon antigen re-encounter. However, IL-12 signaling is not involved in CD8+ Tm cell survival and recall responses. Therefore, this study provides useful information for vaccine design and development.

Development of a toolkit for piggyBac-mediated integrative transfection of the human filarial parasite Brugia malayi.

BACKGROUND: The human filarial parasites cause diseases that are among the most important causes of morbidity in the developing world. The elimination programs targeting these infections rely on a limited number of drugs, making the identification of new chemotherapeutic agents a high priority. The study of these parasites has lagged due to the lack of reverse genetic methods. METHODOLOGY/PRINCIPAL FINDINGS: We report a novel co-culture method that results in developmentally competent infective larvae of one of the human filarial parasites (Brugia malayi) and describe a method to efficiently transfect the larval stages of this parasite. We describe the production of constructs that result in integrative transfection using the piggyBac transposon system, and a selectable marker that can be used to identify transgenic parasites. We describe the production and use of dual reporter plasmids containing both a secreted luciferase selectable marker and fluorescent protein reporters that will be useful to study temporal and spatial patterns of gene expression. CONCLUSIONS/SIGNIFICANCE: The methods and constructs reported here will permit the efficient production of integrated transgenic filarial parasite lines, allowing reverse genetic technologies to be applied to all life cycle stages of the parasite.

IL-10 has a distinct immunoregulatory effect on naive and active T cell subsets.

Interleukin-10 (IL-10) has been identified as a key immunomodulatory cytokine on T cells. However, both immunosuppressive and immunostimulatory effects of IL-10 on T cells also have been reported. The discrepancy between these in vitro effects of IL-10 may be due to the different T cells (naive vs. active or resting active T cells) used under various experimental conditions in these studies. Therefore, it is necessary to clearly define the IL-10 effect on T cell subsets in their different statuses. In this study, we used a molecularly defined T cell system, the ovalbumin (OVA)-specific CD4(+) and CD8(+) T cells from transgenic OT-I and OT-II mice expressing OVA-specific T cell receptor (TCR). We investigated the effect of IL-10 on these OVA-specific T cell subsets in their different statuses (i.e., naive and active T cells). Our data demonstrate that IL-10 has distinct immunoregulatory effects on naive and active T cell subsets. IL-10 inhibits active CD4(+) T cell proliferation, whereas it stimulates and suppresses active CD8(+) T cell proliferation and cytotoxicity, respectively. IL-10-treated dendritic cells (DCs) stimulate anergic cytotoxic T lymphocyte-associated molecule-4 (CTLA)-4-expressing CD4(+) T cell responses possibly through downregulation of major histocompetibility complex (MHC) class II and costimulatory molecule expression on DCs. The anergic CD4(+) T cells suppress T cell proliferation mainly through a CTLA-4-mediated pathway. The distinct role of IL-10 on T cell subsets may be useful in designing T cell-based immunotherapy of cancer and infectious diseases.

Interferon gamma stimulates cellular maturation of dendritic cell line DC2.4 leading to induction of efficient cytotoxic T cell responses and antitumor immunity.

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for the initiation of antigen (Ag)-specific immune responses. In most studies, mature DCs are generated from bone marrow cells or peripheral monocytes; in either case, the harvested cells are then cultured in medium containing recombinant GM-CSF, IL-4 and TNF-alpha for 7-10 days and stimulated with lipopolysaccharide (LPS). However, this approach is time-consuming and expensive. There is another less cost approach of using immobilized DC cell lines, which can easily grow in the medium. A disadvantage with the immobilized DC cell lines, however, is that they are immature DCs and lack expression of MHC class II and costimulatory CD40 and CD80 molecules. This, therefore, limits their capacity for inducing efficient antitumor immunity. In the current study, we investigated the possible efficacy of various stimuli (IL-1beta,IFN-gamma, TNF-alpha, CpG and LPS) in converting the immature dendritic cell line DC2.4 to mature DCs. Our findings were quite interesting since we demonstrated for the first time that IFN-gamma was able to stimulate the maturation of DC2.4 cells. The IFN-gamma-activated ovalbumin (OVA)-pulsed DC2.4 cells have capacity to upregulate MHC class II, CD40, CD80 and CCR7, and to more efficiently stimulate in vitro and in vivo OVA-specific CD8+ T cell responses and antitumor immunity. Therefore, IFN-gamma-activated immortal DC2.4 cells may prove to be useful in the study of DC biology and antitumor immunity.

Type 1 CD8+ T cells are superior to type 2 CD8+ T cells in tumor immunotherapy due to their efficient cytotoxicity, prolonged survival and type 1 immune modulation.

CD8+ cytotoxic T (Tc) cells play a crucial role in host immune responses to cancer, and in this context, adoptive CD8+ Tc cell therapy has been studied in numerous animal tumor models. Its antitumor efficacy is, to a large extent, determined by the ability of Tc cells to survive and infiltrate tumors. In clinical trials, such in vitro-activated T cells often die within hours to days, and this greatly limits their therapeutic efficacy. CD8+ Tc cells fall into two subpopulations based upon their differential cytokine secretion. In this study, we in vitro generated that ovalbumin (OVA)-pulsed dendritic cell (DCOVA)-activated CD8+ type 1 Tc (Tc1) cells secreting IFN-gamma, and CD8+ type 2 Tc (Tc2) cells secreting IL-4, IL-5 and IL-10, which were derived from OVA-specific T cell receptor (TCR) transgenic OT I mice. We then systemically investigated the in vitro and in vivo effector function and survival of Tc1 and Tc2 cells, and then assessed their survival kinetics after adoptively transferred into C57BL/6 mice, respectively. We demonstrated that, when compared to CD8+ Tc2, Tc1 cells were significantly more effective in perforin-mediated cytotoxicity to tumor cells, had a significantly higher capacity for in vivo survival after the adoptive T cell transfer, and had a significantly stronger therapeutic effect on eradication of well-established tumors expressing OVA in animal models. In addition, CD8+ Tc1 and Tc2 cells skewed the phenotype of CD4+ T cells toward Th1 and Th2 type, respectively. Therefore, the information regarding the differential effector function, survival and immune modulation of CD8+ Tc1 and Tc2 cells may provide useful information when preparing in vitro DC-activated CD8+ T cells for adoptive T cell therapy of cancer.

Tumor-infiltrating dendritic cell subsets of progressive or regressive tumors induce suppressive or protective immune responses.

Tumor-infiltrating dendritic cells (TID) have an ambivalent role in regulation of tumor regression or growth. However, their precise natures and molecular mechanisms have not been elucidated. In this study, we studied TIDs recruited in progressive P815 and regressive P198 tumors of the same origin. Our data showed that P815 tumors contained CD4+ 8+ and CD4- 8- TID815 subsets, whereas P198 tumors contained CD4+ 8+ and CD4+ 8- TID198 subsets. They similarly stimulate allogeneic T cell proliferation and have nitric oxide-mediated cytotoxicity to tumor cells with an exception of CD4- 8- TID815 with less efficiency. The newly identified fourth CD4+ 8+ TID815 or TID198 subset and the CD4+ 8- TID198 all express high levels of IFN-gamma and interleukin (IL)-6, whereas CD4- 8- TID815 secrete a marked level of transforming growth factor-beta. Vaccination of mice with P815 tumor lysate-pulsed CD4+ 8+ TID815 or TID198 and CD4+ 8- TID198 induced IFN-gamma-secreting Th1 and effective CTL responses leading to protective immunity against P815 tumor, whereas CD4- 8- TID815 stimulated IL-10-expressing Tr1 responses leading to immune suppression. Transfer of CD4+ Tr1 cells obtained from CD4- 8- TID815-immunized wild-type, but not IL-10(-/-) mice, into CD4+ 8+ TID815 immunized mice abolished otherwise inevitable development of antitumor immunity. Taken together, our findings provide an important insight into immunologic alterations in progressive and regressive tumors and an implication for dendritic cell-based approaches in the design of cancer vaccines.