18 research outputs found
Effective Antigen-Specific Immunotherapy in the Marmoset Model of Multiple Sclerosis
Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates. The Journal of Immunology, 2001, 166: 2116 -2121. M ultiple sclerosis (MS) 4 is a paralytic disease involving destruction of myelin sheaths surrounding axons in the CNS (1, 2). MS affects young adults, most often women residing in northern latitudes. The disease exhibits relapsing and remitting symptoms including disturbances in vision, speech, coordination, and cognition as well as weakness, spasticity, and paralysis (1, 2). Lymphocytic infiltration in the CNS white matter and immune reactions against myelin Ags indicate an autoimmune etiology for MS (1-8). Allergic encephalomyelitis was first observed as a side effect of the rabies vaccine prepared from rabbit brains by Pasteur in the 1880s (see Ref. 3). Rivers and others showed that the CNS inflammation was caused not by the rabies virus but by immune sensitization to the combination of adjuvant and brain tissue contaminating the vaccine (3, 4). Experimental allergic encephalomyelitis (EAE) models in various animal species, typically rodents, were later developed by immunization with myelin proteins in adjuvant or by the adoptive transfer of myelinreactive T cells, causing inflammatory damage to the white matter (1-6). Rodent EAE is the most widely used disease model despite important differences from MS (2). Encephalitogenic CD4 ϩ T cells are believed to initiate and perpetuate EAE and MS and thus constitute a therapeutic target (1-8). Abundant myelin protein Ags, including myelin basic protein (MBP) and proteolipid protein (PLP) as well as the less abundant Ags, myelin oligodendrocyte glycoprotein (MOG) and myelin-associated glycoprotein (MAG), are recognized by T cells in MS patients (9 -11). T cell responses against MBP and PLP may occur at an increased frequency in MS patients compared with controls (1, 2, 11, 12). Ag-specific immunotherapies directed at T cells could avoid the harmful side effects of general immunosuppressive treatments. We have investigated a potential immunotherapy for MS based on our observation that T cells undergo apoptosis both in vitro and in vivo when exposed to high or repeated doses of their cognate Ag (13, To present a broad array of potential epitopes to reactive T cells, we constructed MP4, a protein chimera of the 21.5-kDa isoform of human MBP, and a modified form of human PLP, termed PLP4, that lacks the hydrophobic domains of the protein but includes all of the known T cell epitopes (19 -21). MP4 is processed into multiple determinants and can eliminate rodent EAE by promoting tolerance to different epitopes In a few instances, EAE and Ag treatments have been studied in nonhuman primates. EAE was originally induced in rhesus macaques using CNS homogenates or purified MBP (3, 4, 30 -32). It was also found that repeated injections of MBP could arrest EAE The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact
A Connection between Colony Biomass and Death in Caribbean Reef-Building Corals
Increased sea-surface temperatures linked to warming climate threaten coral reef ecosystems globally. To better understand how corals and their endosymbiotic dinoflagellates (Symbiodinium spp.) respond to environmental change, tissue biomass and Symbiodinium density of seven coral species were measured on various reefs approximately every four months for up to thirteen years in the Upper Florida Keys, United States (1994–2007), eleven years in the Exuma Cays, Bahamas (1995–2006), and four years in Puerto Morelos, Mexico (2003–2007). For six out of seven coral species, tissue biomass correlated with Symbiodinium density. Within a particular coral species, tissue biomasses and Symbiodinium densities varied regionally according to the following trends: Mexico≥Florida Keys≥Bahamas. Average tissue biomasses and symbiont cell densities were generally higher in shallow habitats (1–4 m) compared to deeper-dwelling conspecifics (12–15 m). Most colonies that were sampled displayed seasonal fluctuations in biomass and endosymbiont density related to annual temperature variations. During the bleaching episodes of 1998 and 2005, five out of seven species that were exposed to unusually high temperatures exhibited significant decreases in symbiotic algae that, in certain cases, preceded further decreases in tissue biomass. Following bleaching, Montastraea spp. colonies with low relative biomass levels died, whereas colonies with higher biomass levels survived. Bleaching- or disease-associated mortality was also observed in Acropora cervicornis colonies; compared to A. palmata, all A. cervicornis colonies experienced low biomass values. Such patterns suggest that Montastraea spp. and possibly other coral species with relatively low biomass experience increased susceptibility to death following bleaching or other stressors than do conspecifics with higher tissue biomass levels
Recommended from our members
The Impact of Student Composition on Academic Achievement in Southern High Schools
Recommended from our members
The Impact of Student Composition on Academic Achievement in Southern High Schools
The Efficacy of Common Fit Indices for Enumerating Classes in Growth Mixture Models When Nested Data Structure is Ignored: A Monte Carlo Study
This article investigates whether the correct number of classes can still be retrieved when a higher level of nesting in multilevel growth mixture model (MGMM) is ignored
Recommended from our members
The Hazards of Changing Schools for California Latino Adolescents
Students in the United States are highly mobile. Previous research has shown that the majority of students in the United States change schools between grades 1 and 12 for reasons other than promotion from one level to another (e.g., elementary to middle school.). Research also has found that student mobility is generally detrimental to student achievement. Despite this evidence, the issue of student mobility has not received much attention from educational researchers, practitioners, or policy makers.In this report we examine student mobility among California Latino adolescents. Student mobility may be especially important in California because of its highly mobile population. Latinos are the largest and fastest growing segment of the state population. According to California Department of Finance estimates, the Latino public-school population is projected to triple in size between 1986 and 2006, while the non-Latino public-school population is projected to decrease (see Figure 1.1). Consequently, if student mobility can be problematic for both students and schools, as previous research suggest, it is especially important to understand the nature of mobility among the Latino population.Using longitudinal data on two samples of California students—the first a group of 8th grade students who were surveyed over a sex-year period from 1988 to 1994; and the second a group of low-income, urban Latino 7th grade students who were first studied over a six-year period from 1990 to 1996—this study examined the incidence, causes, and consequences of student mobility, particularly during high school. Throughout this study we examine differences between Latino and non-Latino white students, as well as differences among Latino students. Here we summarize some of the major findings of this study
Recommended from our members
The Hazards of Changing Schools for California Latino Adolescents
Students in the United States are highly mobile. Previous research has shown that the majority of students in the United States change schools between grades 1 and 12 for reasons other than promotion from one level to another (e.g., elementary to middle school.). Research also has found that student mobility is generally detrimental to student achievement. Despite this evidence, the issue of student mobility has not received much attention from educational researchers, practitioners, or policy makers.In this report we examine student mobility among California Latino adolescents. Student mobility may be especially important in California because of its highly mobile population. Latinos are the largest and fastest growing segment of the state population. According to California Department of Finance estimates, the Latino public-school population is projected to triple in size between 1986 and 2006, while the non-Latino public-school population is projected to decrease (see Figure 1.1). Consequently, if student mobility can be problematic for both students and schools, as previous research suggest, it is especially important to understand the nature of mobility among the Latino population.Using longitudinal data on two samples of California students—the first a group of 8th grade students who were surveyed over a sex-year period from 1988 to 1994; and the second a group of low-income, urban Latino 7th grade students who were first studied over a six-year period from 1990 to 1996—this study examined the incidence, causes, and consequences of student mobility, particularly during high school. Throughout this study we examine differences between Latino and non-Latino white students, as well as differences among Latino students. Here we summarize some of the major findings of this study