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11.
CTLA-4 is required for the induction of high dose oral tolerance 总被引:5,自引:3,他引:5
Samoilova EB; Horton JL; Zhang H; Khoury SJ; Weiner HL; Chen Y 《International immunology》1998,10(4):491-498
Mucosal and systemic administrations of high dose antigens induce long-
lasting peripheral T cell tolerance. We and others have shown that high
dose peripheral T cell tolerance is mediated by anergy or deletion and is
preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2
(CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell
activation and immune regulation. In the present study, we examined the
roles of the B7 co-stimulation pathway in the generation of high dose
peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4
interaction at the time of tolerance induction partially prevented T cell
tolerance, whereas selective blockade of B7:CTLA-4 interaction completely
abrogated peripheral T cell tolerance induced by either oral or i.p.
antigens. These results suggest that CTLA-4-mediated feedback regulation
plays a crucial role in the induction of high dose peripheral T cell
tolerance.
相似文献
12.
Molecular genetic characterization of XRCC4 function 总被引:2,自引:0,他引:2
XRCC4 is a generally expressed protein of 334 amino acids that is involved
in the repair of DNA double-strand breaks and in V(D)J recombination, but
its function is unknown. In this study, we have used a mutational approach
and the yeast two-hybrid method to perform an initial characterization of
this protein. We show that the XRCC4 protein is located in the nucleus. We
also demonstrate that several potential phosphorylation sites are not
required for XRCC4 function in a transient V(D)J recombination assay. In
addition, we show that XRCC4 forms a homodimer in vivo with the
homodimerization domain being located within amino acids 115-204. Finally,
we define a core domain of XRCC4 that functions in V(D)J recombination and
comprises amino acids 18-204. Potential functions of XRCC4 are discussed.
相似文献
13.
Liu JQ; Bai XF; Shi FD; Xiao BG; Li HL; Levi M; Mustafa M; Wahren B; Link H 《International immunology》1998,10(8):1139-1148
Induction of mucosal tolerance by inhalation of soluble peptides with
defined T cell epitopes is receiving much attention as a means of
specifically down-regulating pathogenic T cell reactivities in autoimmune
and allergic disorders. Experimental autoimmune encephalomyelitis (EAE)
induced in the Lewis rat by immunization with myelin basic protein (MBP)
and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the
MBP amino acid sequences 68-86 and 87-99. To further define the principles
of nasal tolerance induction, we generated three different MBP peptides
(MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and
evaluated whether their nasal administration on day -11, -10, -9, -8 and -7
prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection
to Lewis rat EAE. Protection was achieved with the encephalitogenic
peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP
110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete
protection to gp-MBP-induced EAE. In contrast, nasal administration of a
mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even
at lower dosage compared to that being used for individual peptides. Rats
tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses
to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays.
Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive
IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node
cells compared to rats receiving MBP 110-128 nasally, while similar low
levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA
expressing cells were observed in the two groups. Nasal administration of
MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord
homogenate-induced EAE, and passive transfer of spleen mononuclear cells
from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE.
Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse
ongoing EAE induced with gp-MBP, although higher doses are required
compared to the dosage needed for prevention. In conclusion, nasal
administration of encephalitogenic MBP peptides can induce antigen-specific
T cell tolerance and confer incomplete protection to gp-MBP-induced EAE,
and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms
are proposed to be responsible for tolerance development after nasal
peptide administration.
相似文献
14.
The relationship between demographic factors and attitudes toward mental health services. 总被引:3,自引:0,他引:3
Considerable effort has been exerted in recent years toward educating the public concerning mental illness and the efficacy of various treatment modalities. Most previous studies of attitudes have focused solely on attitudes toward the mentally ill. In this study we investigated attitudes toward mental health services and found that most people are positively disposed toward the use of these services. Attitudes toward the use of mental health services were affected by the age, sex, race, education, and income of the subjects. In general, differences of attitude lie in the direction that would tend to inhibit utilization among those most at risk. 相似文献
15.
16.
Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids 总被引:1,自引:0,他引:1
Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids. 相似文献
17.
Targeted delivery remains the major challenge for the application of small interfering RNA (siRNA). We have developed a lipid/calcium/phosphate (LCP) nanoparticle (NP) to improve siRNA delivery efficiency. The LCP NP was prepared by using microemulsion technology to form calcium/phosphate (CaP) core and further coated with cationic lipids. The final NP was grafted with polyethylene glycol (PEG) and anisamide (AA) ligand on the surface to target sigma receptor-expressing B16F10 melanoma cells. The LCP NP exhibited a 40 nm particle size, a +25 mV zeta-potential, and 91% siRNA encapsulation efficiency. After a single intravenous (i.v.) injection of antiluciferase siRNA (0.12 mg siRNA/kg) formulated in targeted LCP NP, luciferase activity in metastatic B16F10 tumor-loaded lungs decreased by 78% in C57BL/6 mice. In a therapeutic experiment, siRNA against MDM2, c-myc, and VEGF coformulated in the targeted LCP NP resulted in simultaneous silencing of the respective oncogenes in metastatic nodules. Treatment with siRNA in the targeted NP significantly reduced lung metastases (~70–80%) at a relatively low dose (0.36 mg/kg), whereas control group showed little therapeutic effect. Moreover, this targeted LCP NP significantly prolonged the mean survival time of the animals by 27.8% compared to control group without showing any toxicity at the therapeutic dose. 相似文献
18.
Cationic lipid- and polymer-based vectors are the most extensively studied synthetic gene vectors. These vectors have been widely used in animal models and some have been tested in clinical trials. The clinical progress of these vectors has been slowed by their inflammatory toxicity. This review summarizes the observations, the mechanisms, and various strategies employed to overcome the inflammatory toxicity of cationic gene vectors. 相似文献
19.
Elizabeth McFarlane Lori Burrell Sarah Crowne Fallon Cluxton-Keller Loretta Fuddy Philip J. Leaf Anne Duggan 《Prevention science》2013,14(1):25-39
There is variability in home visiting program impacts on the outcomes achieved by high risk families. An understanding of how effects vary among families is important for refining service targeting and content. The current study assessed whether and how maternal attributes, including relationship security, moderate short- and long-term home visiting impacts on maternal psychosocial functioning. In this multisite RCT of home visiting in a population-based, ethnically-diverse sample of families at risk for maltreatment of their newborns (n?=?643), families were randomly assigned to home visited (HV) and control groups. HV families were to receive intensive services by trained paraprofessionals from birth-3 years. Outcome data were collected when children were 1, 2, and 3 years old and 7, 8, and 9 years old. Overall, short- and long-term outcomes for HV and control mothers did not differ significantly. Demographic attributes, a general measure of overall maternal risk, and partner violence did not moderate program impact on psychosocial functioning outcomes. Maternal relationship security did moderate program impact. Mothers who scored high on relationship anxiety but not on relationship avoidance showed the greatest benefits, particularly at the long-term follow-up. Mothers scoring high for both relationship anxiety and avoidance experienced some adverse consequences of home visiting. Further research is needed to determine mediating pathways and to inform and test ways to improve the targeting of home visiting and the tailoring of home visit service models to extend positive home visiting impacts to targeted families not benefiting from current models. 相似文献
20.