Similar Datasets
Project description:Early life environmental exposure, particularly during perinatal period, can have a lifelong impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptation to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitaryadrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.
2020-01-01 | GSE136972 | GEO
Project description:Early life environmental exposure, particularly during perinatal period, can have a lifelong impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptation to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitaryadrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.
2020-01-01 | GSE136978 | GEO
Project description:Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.
| S-EPMC7399609 | biostudies-literature
Project description:Long-term programming of CD8 T cell immunity by perinatal exposure to stress hormone
| PRJNA564143 | ENA
Project description:Long-term programming of CD8 T cell immunity by perinatal exposure to stress hormone [ATAC-seq]
| PRJNA564138 | ENA
Project description:Long-term programming of CD8 T cell immunity by perinatal exposure to stress hormone [RNA-seq]
| PRJNA564147 | ENA
Project description:Thyroid hormones are critical for mammalian brain development. Thus, chemicals that can affect thyroid hormone signaling during pregnancy are of great concern. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, breastmilk, and other tissues, capable of lowering serum thyroxine (T4) in rats. Here, we investigated its effects on the thyroid system and neurodevelopment following maternal exposure from early gestation through lactation (0.05, 5 or 25 mg/kg/day PFHxS), alone or in combination with a mixture of 12 environmentally relevant endocrine disrupting compounds (EDmix). PFHxS lowered thyroid hormone levels in both dams and offspring in a dose-dependent manner, but did not change TSH levels, weight, histology, or expression of marker genes of the thyroid gland. No evidence of thyroid hormone-mediated neurobehavioral disruption in offspring was observed. Since human brain development appear very sensitive to low T4 levels, we maintain that PFHxS is of potential concern to human health. It is our view that current rodent models are not sufficiently sensitive to detect adverse neurodevelopmental effects of maternal and perinatal hypothyroxinemia and that we need to develop more sensitive brain-based markers or measurable metrics of thyroid hormone-dependent perturbations in brain development.
| S-EPMC7021709 | biostudies-literature
Project description:We developed an innovative method to induce antigen-specific CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). This approach employs a DNA vector expressing a mutated HIV-1 Nef protein (Nefmut) deprived of the anti-cellular effects typical of the wild-type isoform, meanwhile showing an unusual efficiency of incorporation into EVs. This function persists even when foreign antigens are fused to its C-terminus. In this way, Nefmut traffics large amounts of antigens fused to it into EVs spontaneously released by the recipient cells. We previously provided evidence that mice injected with a DNA vector expressing the Nefmut/HPV16-E7 fusion protein developed an E7-specific CTL immune response as detected 2 weeks after the second immunization. Here, we extended and optimized the anti-HPV16 CD8+ T cell immune response induced by the endogenously engineered EVs, and evaluated the therapeutic antitumor efficacy over time. We found that the co-injection of DNA vectors expressing Nefmut fused with E6 and E7 generated a stronger anti-HPV16 immune response compared to that observed in mice injected with the single vectors. When HPV16-E6 and -E7 co-expressing tumor cells were implanted before immunization, all mice survived at day 44, whereas no mice injected with either void or Nefmut-expressing vectors survived until day 32 after tumor implantation. A substantial part of immunized mice (7 out of 12) cleared the tumor. When the cured mice were re-challenged with a second tumor cell implantation, none of them developed tumors. Both E6- and E7-specific CD8+ T immunities were still detectable at the end of the observation time. We concluded that the immunity elicited by engineered EVs, besides counteracting and curing already developed tumors, was strong enough to guarantee the resistance to additional tumor attacks. These results can be of relevance for the therapy of both metastatic and relapsing tumors.
| S-EPMC8125873 | biostudies-literature
Project description:A method to genetically program mouse hematopoietic stem cells to develop into functional CD8 or CD4 T cells of defined specificity in vivo is described. For this purpose, a bicistronic retroviral vector was engineered that efficiently delivers genes for both alpha and beta chains of T cell receptor (TCR) to hematopoietic stem cells. When modified cell populations were used to reconstruct the hematopoietic lineages of recipient mice, significant percentages of antigen-specific CD8 or CD4 T cells were observed. These cells expressed normal surface markers and responded to peptide antigen stimulation by proliferation and cytokine production. Moreover, they could mature into memory cells after peptide stimulation. Using TCRs specific for a model tumor antigen, we found that the recipient mice were able to partially resist a challenge with tumor cells carrying the antigen. By combining cells modified with CD8- and CD4-specific TCRs, and boosting with dendritic cells pulsed with cognate peptides, complete suppression of tumor could be achieved and even tumors that had become established would regress and be eliminated after dendritic cell/peptide immunization. This methodology of "instructive immunotherapy" could be developed for controlling the growth of human tumors and attacking established pathogens.
| S-EPMC553287 | biostudies-literature
Project description:A slow embryonic heart rate in early-mid gestation is associated with increased risk of embryonic death and malformation, however, the long-term consequences remain unknown. We administered Dofetilide (Dof, 2.5 mg/kg), a drug that produces embryo-specific bradycardia, to pregnant rats from gestational days 11-14. Embryonic heart rate and rhythm were determined using embryo culture. Cardiovascular function was assessed in surviving adult offspring at rest, during acute psychological stress (air jet stress, AJS), and after 7 days of repeated AJS. Dof reduced embryonic HR by 40% for ~8 h on each of the treatment days. On postnatal day 3, Dof offspring were ~10% smaller. Blood pressure was elevated in adult Dof rats (systolic blood pressure, night: 103.8 ± 3.9 vs. 111.2 ± 3.0 mmHg, P = 0.01). While the pressor response to AJS was similar in both groups (control 17.7 ± 3.4; Dof 18.9 ± 0.9 mmHg, P = 0.74), after 7 days repeated AJS, clear habituation was present in control (P = 0.0001) but not Dof offspring (P = 0.48). Only Dof offspring showed a small increase in resting blood pressure after 7 days repeated stress (+3.9 ± 1.7 mmHg, P = 0.05). The results indicate that embryonic bradycardia programs hypertension and impaired stress adaptation, and have implications for the maternal use of cardioactive drugs during pregnancy.
| S-EPMC5835481 | biostudies-literature