Solid organ transplantation remains the life-saving treatment for end-stage organ failure, but chronic rejection remains a major obstacle to long-term allograft outcomes and has not improved substantially. Tertiary lymphoid organs (TLOs) are ectopic lymphoid structures that form under conditions of chronic inflammation, and evidence from human transplantation suggests that TLOs regularly form in allografts undergoing chronic rejection. In this study, we utilized a mouse renal transplantation model and manipulation of the lymphotoxin αβ/lymphotoxin β receptor (LTαβ/LTβR) pathway, which is essential for TLO formation, to define the role of TLOs in transplantation.
View Article and Find Full Text PDFGlomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges.
View Article and Find Full Text PDFOur understanding of tissue-resident memory T (T) cell biology has been largely developed from acute infection models in which antigen is cleared and sterilizing immunity is achieved. Less is known about T cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie T maintenance in a kidney transplantation model in which T cells drive rejection.
View Article and Find Full Text PDFAccess to field experiences can increase participation of diverse groups in the environmental and natural resources (ENR) workforce. Despite a growing interest among the ENR community to attract and retain diverse students, minimal data exist on what factors undergraduate students prioritize when applying for field experiences. Using a nationwide survey of US undergraduate ENR students, we show that attracting most students to field experiences-especially racial or ethnic minority students-will require pay above minimum wage.
View Article and Find Full Text PDFTissue-resident memory T cells (T) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells.
View Article and Find Full Text PDFImmunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. However, it is unknown whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously on subsequent encounters. In this work, we show that murine monocytes and macrophages acquire memory specific to major histocompatibility complex I (MHC-I) antigens, and we identify A-type paired immunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response.
View Article and Find Full Text PDFis a bacterial symbiont that colonizes the light organ of the Hawaiian bobtail squid, Certain strains of express a type VI secretion system (T6SS), which delivers effectors into neighboring cells that result in their death. Strains that are susceptible to the T6SS fail to establish symbiosis with a T6SS-positive strain within the same location of the squid light organ, which is a phenomenon termed strain incompatibility. This study investigates the regulation of the T6SS in strain FQ-A001.
View Article and Find Full Text PDFActivation of host T cells that mediate allograft rejection is a 2-step process. The first occurs in secondary lymphoid organs where T cells encounter alloantigens presented by host DCs and differentiate to effectors. Antigen presentation at these sites occurs principally via transfer of intact, donor MHC-peptide complexes from graft cells to host DCs (cross-dressing) or by uptake and processing of donor antigens into allopeptides bound to self-MHC molecules (indirect presentation).
View Article and Find Full Text PDFThe aim of this study was to identify lifestyle profiles of young adult males and females based on their alcohol, diet, and exercise behaviors and then link these profiles with health. We used the nationally representative 2017 Behavioral Risk Factor Surveillance System (BRFSS; N = 17,286; 47% female; M = 23.22; SD = 3.
View Article and Find Full Text PDFBacteria that have the capacity to fill the same niche will compete with one another for the space and resources available within an ecosystem. Such competition is heightened among different strains of the same bacterial species. Nevertheless, different strains often inhabit the same host.
View Article and Find Full Text PDFBackground: Few studies use longitudinal designs to assess patterns of body mass index (BMI) change from adolescence to adulthood or incorporate severe obesity as a unique subgroup.
Objective: To examine patterns of BMI trajectories from adolescence to adulthood and identify demographic characteristics associated with each BMI trajectory pattern.
Design: Height, weight, and demographic characteristics were drawn from Waves I to V of the nationally representative school-based sample of the National Longitudinal Study of Adolescent to Adult Health (Add Health) conducted from 1994 to 2018 (data collection is ongoing).
Mice devoid of T, B, and natural killer (NK) cells distinguish between self and allogeneic nonself despite the absence of an adaptive immune system. When challenged with an allograft, they mount an innate response characterized by accumulation of mature, monocyte-derived dendritic cells (DCs) that produce interleukin-12 and present antigen to T cells. However, the molecular mechanisms by which the innate immune system detects allogeneic nonself to generate these DCs are not known.
View Article and Find Full Text PDFSuccessful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells.
View Article and Find Full Text PDFBony fish are among the first vertebrates to possess an innate and adaptive immune system. In these species, the kidney has a dual function: filtering solutes similar to mammals and acting as a lymphoid organ responsible for hematopoiesis and antigen processing. Recent studies have shown that the mammalian kidney has an extensive network of mononuclear phagocytes, whose function is not fully understood.
View Article and Find Full Text PDFPancreatic islet transplantation is a promising therapy for diabetes, but acute rejection of the islets by host effector T cells has hindered clinical application. In this study, we addressed the mechanisms of CD8(+) effector T cell migration to islet grafts because interrupting this step is key to preventing rejection. We found that effector T cell migration to revascularized islet transplants in mice is dependent on non-self Ag recognition rather than signaling via Gαi-coupled chemokine receptors.
View Article and Find Full Text PDFUnlabelled: Background Women's risk for sexually transmitted diseases (STDs) were examined in terms of adolescent and young adult weight status, self-esteem trajectories and weight contentment using two waves of a nationally representative dataset.
Methods: Using Waves 1 and 3 of the National Longitudinal Study of Adolescent Health, body mass index (BMI), self-esteem and weight contentment were examined during adolescence and young adulthood to assess the likelihood of STDs among 4000 young adult single women.
Results: Change in BMI, specifically weight loss between adolescence and young adulthood, significantly increased women's risk for STDs.
Maturation of T cell-activating APCs directly links innate and adaptive immunity and is typically triggered by microbial infection. Transplantation of allografts, which are sterile, generates strong T cell responses; however, it is unclear how grafts induce APC maturation in the absence of microbial-derived signals. A widely accepted hypothesis is that dying cells in the graft release "danger" molecules that induce APC maturation and initiate the adaptive alloimmune response.
View Article and Find Full Text PDFFamily stress models illustrate how communities affect youth outcomes through effects on parents and studies consistently show the enduring effects of early community context. The present study takes a different approach identifying human agency during adolescence as a potentially significant promotive factor mediating the relationship between community, parenting, and mental health. While agency is an important part of resilience, its longitudinal effects are unknown, particularly based on gender and race/ethnicity.
View Article and Find Full Text PDFThe migration of effector or memory T cells to the graft is a critical event in the rejection of transplanted organs. The prevailing view is that the key steps involved in T cell migration - integrin-mediated firm adhesion followed by transendothelial migration - are dependent on the activation of Gαi-coupled chemokine receptors on T cells. In contrast to this view, we demonstrated in vivo that cognate antigen was necessary for the firm adhesion and transendothelial migration of CD8+ effector T cells specific to graft antigens and that both steps occurred independent of Gαi signaling.
View Article and Find Full Text PDFObjective: To examine valuation of life, loneliness, and depressed mood as mediating the association between age and race/ethnicity and health outcomes among older adult male prisoners.
Methods: Survey of 261 male prisoners ages 45-80 from 8 Oklahoma correctional facilities.
Results: African American prisoners report fewer health conditions than White prisoners - a finding mediated by significantly greater valuation of life, less loneliness, and lower depressed mood among African American prisoners.
Background: Acute allograft rejection is dependent on adaptive immunity, but it is unclear whether the same is true for chronic rejection. Here we asked whether innate immunity alone is sufficient for causing chronic rejection of mouse cardiac allografts.
Methods: We transplanted primarily vascularized cardiac grafts to recombinase activating gene-knockout (RAG(-/-)) mice that lack T and B cells but have an intact innate immune system.
Background: Memory T cells migrate to and reject transplanted organs without the need for priming in secondary lymphoid tissues, but the mechanisms by which they do so are not known. Here, we tested whether CXCR3, implicated in the homing of effector T cells to sites of infection, is critical for memory T-cell migration to vascularized allografts.
Methods: CD4 and CD8 memory T cells were sorted from alloimmunized CXCR3 and wildtype B6 mice and cotransferred to congenic B6 recipients of BALB/c heart allografts.
Background: Breakfast consumption is often examined when researching adolescent dietary intakes and overall health. However, fewer studies have examined the relationship between breakfast and obesity, particularly over time and in relation to weight outcomes in young adulthood. In addition, little is known about contextual factors influencing the likelihood of adolescents consuming breakfast on a regular basis.
View Article and Find Full Text PDFThe clinical utility of the Medical Symptom Validity Test (MSVT) for soldiers returning from service in Operation Iraqi Freedom or Operation Enduring Freedom was preliminarily investigated through retrospective chart review. Results showed that 17%, or 4 of 23, Operation Iraqi Freedom/Operation Enduring Freedom patients at a Polytrauma Network Site (Level 2), performed below cut-offs on the MSVT. On "easy" subtests of the MSVT, the group of individuals who failed the MSVT performed significantly worse than the group of individuals who passed.
View Article and Find Full Text PDFThis study explored content posted and interactions taking place on adolescent online social networking profiles. Although "blogging" continues to soar in popularity, with over half of teenagers online participating in some form, little research has comprehensively explored blog communication within the context of adolescent development. Content was qualitatively coded from 100 randomly selected profiles authored by adolescents between the ages of 16 and 18.
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