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Kundel HL; Gefter W; Aronchick J; Miller W Jr; Hatabu H; Whitfill CH; Miller W Sr 《Radiology》1997,205(3):859
4.
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
5.
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
6.
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
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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
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Alison J. Wright Sophia C. L. Whitwell Chika Takeichi Matthew Hankins Theresa M. Marteau 《British journal of health psychology》2009,14(1):107-125
Objectives. Numeracy, the ability to process basic mathematical concepts, may affect responses to graphical displays of health risk information. Displays of probabilistic risk information using grouped dots are easier to understand than displays using dispersed dots. However, dispersed dots may better convey the randomness with which health threats occur, so increasing perceived susceptibility. We hypothesized that low numeracy participants would better understand risks presented using grouped dot displays, while high numeracy participants would have good understanding, regardless of display type. Moreover, we predicted that dispersed dot displays, in contrast to grouped dot displays, would increase risk perceptions and worry only for highly numerate individuals. Design and method. One hundred and forty smokers read vignettes asking them to imagine being at risk of Crohn's disease, in a 2(display type: dispersed/grouped dots)×3(risk magnitude: 3%/6%/50%)×2(numeracy: high/low) design. They completed measures of risk comprehension, perceived susceptibility and worry. Results. More numerate participants had better objective risk comprehension, but this effect was not moderated by display type. There was marginally significant support for the predicted numeracy × display type interaction for worry about Crohn's disease, but not for perceived susceptibility to the condition. Conclusions. Dispersed dot displays somewhat increase worry in highly numerate individuals, but only numeracy influenced objective risk comprehension. The most effective display type for communicating risk information will depend on the numeracy of the population and the goal(s) of the communication. 相似文献