Altered serological and cellular reactivity to H-2 antigens after target cell infection with vaccinia virus

MICE generate cytotoxic T lymphocytes (CTL) which are able to lyse virus infected target cells in vitro after infection with lymphocytic choriomeningitis virus (LCMV) and pox-viruses1−3. CTL kill syngeneic and semiallogenic infected cells but not allogenic infected targets. Target cell lysis in these systems seems to be restricted by H-2 antigens, especially by the K or D end of the major histocompatibility complex (MHC). In experiments where virus specific sensitised lymphocytes kill virus infected allogenic target cells4 the effector lymphocytes have not been characterised exactly. Recent investigations suggest that the active cell in this assay, at least in the measles infection, is a non-thymus derived cell (H. Kreth, personal communication). An H-2 restriction of cell mediated cytolysis (CMC) to trinitrophenol (TNP)-modified lymphocytes has also been described5. Zinkernagel and Doherty6 postulated that the CTL is directed against syngeneic H-2 antigens and viral antigens and they suggested an alteration of H-2 induced by the LCMV infection. Earlier7 we found a close topological relationship between H-2 antigens and the target antigen(s) responsible for CMC in the vaccinia system. Here we report experiments which were carried out to prove alteration of H-2 after infection of L-929 fibroblasts with vaccinia virus

Reliability of self-report of health in juvenile offenders

The aim of the present study was to investigate the accuracy of self-reports of juvenile offenders on physical factors (e.g., sleep difficulties, weight related behaviors and weight perceptions), health risk behaviors (e.g., alcohol use), trauma history (e.g., physical and sexual abuse) and psychological factors (e.g., anxiety, suicidal and self-harm behaviors). Self-reports obtained via a Health Questionnaire from 242 incarcerated juvenile offenders were compared with standardized measures (Body Mass Index, Adolescent Psychopathology Scale and Child Trauma Questionnaire) to investigate the reliability (via construct validity) and veracity of their self-report. Using kappa estimates and receiver operating characteristic curves, results generally showed high agreement across measures, suggesting that self-report questions from the health survey could all be used reliably. The degree of accuracy indicated that young offenders are as reliable as clinical and community samples of adolescents in their self-report. These findings have implications for routine assessments and practice evaluations that rely on self-report as the method of data collection and as the basis for clinical formulation and treatment planning

Passive experimental autoimmune encephalomyelitis in C57BL/6 with MOG: evidence of involvement of B cells

Experimental autoimmune encephalomyelitis (EAE) is the most relevant animal model to study demyelinating diseases such as multiple sclerosis. EAE can be induced by active (active EAE) or passive (at-EAE) transfer of activated T cells in several species and strains of rodents. However, histological features of at-EAE model in C57BL/6 are poorly described. The aim of this study was to characterize the neuroinflammatory and neurodegenerative responses of at-EAE in C57BL/6 mice by histological techniques and compare them with that observed in the active EAE model. To develop the at-EAE, splenocytes from active EAE female mice were harvested and cultured in presence of MOG 35-55 and IL-12, and then injected intraperitoneally in recipient female C57BL6/J mice. In both models, the development of EAE was similar except for starting before the onset of symptoms and presenting a higher EAE cumulative score in the at-EAE model. Spinal cord histological examination revealed an increased glial activation as well as more extensive demyelinating areas in the at-EAE than in the active EAE model. Although inflammatory infiltrates composed by macrophages and T lymphocytes were found in the spinal cord and brain of both models, B lymphocytes were significantly increased in the at-EAE model. The co-localization of these B cells with IgG and their predominant distribution in areas of demyelination would suggest that IgG-secreting B cells are involved in the neurodegenerative processes associated with at-EAE

Erythropoietin: A potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE

Background: Beneficial effects of short-term erythropoietin (EPO) theraphy have been demonstrated in several animal models of acute neurologic injury, including experimental autoimmune encephalomyelitis(EAE)-the animal model of multiple sclerosis. We have found that EPO treatment substantially reduces the acute clinical paralysis seen EAE mice and this improvements is accompanied by a large reduction in the mononuclear cell infiltration and downregulation of glial MHC class II expression within the inflamed CNS. Other reports have recently indicated that peripherally generated anti-inflammatory CD4 +Foxp3 3 regulatory T cells (Tregs) and the IL17-producing CD4+ T helper cell (Th17) subpopulations play key antagonistic roles in EAE pathogenesis. However, no information regardind the effects of EPO theraphy on the behavior of the general mononuclear-lymphocyte population, Tregs or Th17 cells in EAE has emerged. Methods and Findings: We first determined in vivo that EPO theraphy markedly suppressed MOG specific T cell proliferation and sharply reduced the number of reactive dendritic cells (CD11c positive) in EAE lumph modes during both inductive and later symptomatic phases of MOG 35-55 induced EAE. We then determined the effect in vivo of EPO on numbers of peripheral Treg cells and Th17 cells. We found that EPO treatment modulated immune balance in both the periphery and the inflamed spinal cord by promoting a large expansion in Treg cells, inhibiting Th17 polarization and abrogating proliferation of the antigen presenting dendritic cell population. Finally we utilized tissue culture assays to show that exposure to EPO in vitro similarly downregulated MOG-specific T cell proliferation and also greatly suppressed T cell production of pro-inflammatory cytokines. Conclusions: Taken together, our findings reveal an important new locus whereby EPO induces substantial long-term tissue protection in the host through signalling to several critical subsets of immune cells that reside in the peripheral lymphatic system.published_or_final_versio

“The world around me”: The environment and single women

The “environment” has often been taken as a backdrop for feminist research and theory, as a setting within which issues of feminist concern are played out. This environment, however, is not a neutral setting; rather, research over the past 15 years has evidenced the assumptions about “a woman's place” as a man's wife literally built into women's worlds. Space speaks, and the stories it tells center around particular and identifiable assumptions about gender and where a woman “should” be, when, and with whom. Unmarried women are in a unique position in this environment: they are subjected not only to the economic disadvantages and social subjugation of being a woman, but also to the social and economic drawbacks of being single in a couple-oriented society and in an environment they see as not built for them. Although research exists on the sexism in the physical environment, on women's economic and social position, and on singlehood, a need exists to bridge these areas to explore how single women experience their singlehood, their womanhood, and the environment in their everyday lives and decision making. I conducted in-depth interviews with 25 single women, 23 white and 2 African-American women, about their experiences of living single. This article, based on the results of those interviews and a series of focus group discussions, examines how single women negotiate and respond to their necessary environmental decisions about housing, transportation, and leisure activities in an environment not likely to be conducive to their ways of life.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45605/1/11199_2005_Article_BF01544591.pd

The unfinished legacy of liver transplantation: Emphasis on immunology

Liver transplantation radically changed the philosophy of hepatology practice, enriched multiple areas of basic science, and had pervasive ripple effects in law, public policy, ethics, and theology. Why organ engraftment was feasible remained enigmatic, however, until the discovery in 1992 of donor leukocyte microchimerism in long-surviving liver, and other kinds of organ recipients. Following this discovery, the leukocyte chimerism-associated mechanisms were elucidated that directly linked organ and bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. We describe here how the initially controversial paradigm shift mandated revisions of cherished dogmas. With the fresh insight, the reasons for numerous inexplicable phenomena of transplantation either became obvious or have become susceptible to discriminate experimental testing. The therapeutic implications of the "new immunology" in hepatology and in other medical disciplines, have only begun to be explored. Apart from immunology, physiologic investigations of liver transplantation have resulted in the discovery of growth factors (beginning with insulin) that are involved in the regulation of liver size, ultrastructure, function, and the capacity for regeneration. Such studies have partially explained functional and hormonal relationships of different abdominal organs, and ultimately they led to the cure or palliation by liver transplantation of more than 2 dozen hepatic-based inborn errors of metabolism. Liver transplantation should not be viewed as a purely technologic achievement, but rather as a searchlight whose beams have penetrated the murky mist of the past, and continue to potentially illuminate the future. Copyright © 2006 by the American Association for the Study of Liver Diseases