共查询到20条相似文献,搜索用时 31 毫秒
1.
Kristi Baker Timo Rath Wayne I. Lencer Edda Fiebiger Richard S. Blumberg 《Cellular and molecular life sciences : CMLS》2013,70(8):1319-1334
IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4+ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8+ T cells. 相似文献
2.
M. L. Rose 《Cellular and molecular life sciences : CMLS》1998,54(9):965-978
The immunological properties of human endothelial cells suggest they perform a pivotal role in acute and chronic rejection
following solid organ transplantation. In this review the basic features of acute and chronic rejection are described as are
the cellular and molecular requirements for antigen presentation. Traditionally, antigen-presenting cells are considered to
be bone marrow-derived cells. However, these conclusions have been derived from rodent models of allograft rejection where
bone marrow-derived passenger leukocytes are the only source of donor major histocompatibility complex (MHC) class II in the
grafted organ. In contrast, in humans, virtually all the microvascular and small vessel endothelial cells are ‘constitutively’
positive for MHC class II antigens. The phenotypic properties of human endothelial cells, their response to cytokines and
their ability to stimulate resting T cells are described. Unlike bone marrow-derived antigen presenting cells (APCs), which
utilise B7/CD28 interactions, human endothelial cells utilise lymphocyte function antigen 3 (LFA3)/CD2 pathways to stimulate
T cells. They activate a CD45RO + B7-independent subpopulation of T cells. Their effect on allogeneic T cells is compared
with other non-bone marrow-derived cells such as fibroblasts, epithelial cells and smooth muscle cells, which are unable to
stimulate resting T cells. Evidence is presented suggesting that release of MHC and non-human leukocyte antigens (HLA) from
endothelial cells stimulates an alloantibody and autoimmune response leading to chronic rejection.
Received 30 March 1998; received after revision 4 May 1998; accepted 4 May 1998 相似文献
3.
High frequency of human cytomegalovirus (HCMV)-specific CD8+-T cells detected in a healthy CMV-seropositive donor 总被引:2,自引:0,他引:2
Lang KS Moris A Gouttefangeas C Walter S Teichgräber V Miller M Wernet D Hamprecht K Rammensee HG Stevanovic S 《Cellular and molecular life sciences : CMLS》2002,59(6):1076-1080
Human cytomegalovirus (HCMV) persists after infection but is controlled by cellular immune responses, particularly by CD8+ T cells. If infected individuals are immunosuppressed, HCMV can be reactivated. Upon testing the blood of healthy donors
with human lymphocyte antigen tetramers, we found one individual with about 50 % of his CD8+ T cells being specific for the immunodominant pp65 epitope NLVPMVATV. Over a period of 2 years the high level of HCMV-specific
T cells was maintained, and no HCMV DNA could be detected. At one timepoint, however, HCMV-specific DNA was detected, while
65 % of CD8+ T cells were specific for HCMV. When virus was detectable, a lower percentage of HCMV-specific CD8+ T cells showed interferon γ (IFN-γ) production after peptide stimulation in vitro. These data suggest that HCMV reactivation
may also occur in immunocompetent persons, accompanied by the presence of HCMV-specific CD8+ T cells which are not producing IFNγ, and therefore potentially anergic or in vivo exhausted.
Received 6 March 2002; received after revision 15 April 2002; accepted 17 April 2002 相似文献
4.
T cell activation is enhanced by the costimulatory interaction of B7 on antigen-presenting cells and CD28 on T cells, resulting
in long-term T cell proliferation, differentiation and production of large amounts of cytokines, such as interleukin (IL)-2.
CTLA-4 is a co-stimulation receptor that shares 31% homology with CD28 and binds B7 family members with higher affinity. CTLA-4
is transiently expressed intracellularly and on the cell surface following activation of T cells. We have studied the kinetics
of CTLA-4 expression and the effects of dexamethasone on CTLA-4 expression during T cell activation in cultures of mouse spleen
cells stimulated by a mixture of immobilized anti-CD3 and anti-CD28 monoclonal antibodies (anti-CD3/CD28 mAb) or concanavalin
A (ConA). CTLA-4 expression peaked on day 2 and returned to background levels after 7 days. Dexamethasone was found to potentiate
CTLA-4 expression in a dose-dependent manner with an EC50 effective concentration 50%) of about 10−8 M. In contrast, other immunosuppressive agents, such as rapamycin or cyclosporin A had no or an inhibitory effect on CTLA-4
expression, respectively. Dexamethasone also stimulated CD28 expression, but inhibited IL-2R expression during anti-CD3/CD28
mAb-induced mouse splenic T cell activation. Western blot analyses of lysates of activated mouse T cells showed that dexamethasone
increased CTLA-4 protein levels twofold during anti-CD3/CD28 mAb-induced activation. Dexamethasone also enhanced CTLA-4 messenger
RNA twofold as quantified by ribonuclease protection assay. The effects of dexamethasone on CTLA-4 expression were glucocorticoid-specific
and completely inhibited by the glucocorticoid receptor antagonist mifepristone (RU486), indicating that the effect of dexamethasone
on CTLA-4 expression is mediated through the glucocorticoid receptor. In conclusion, the immunosuppressive agent dexamethasone
actually stimulates CTLA-4 expression, which is involved in downregulation of T cell activation.
Received 19 May 1999; received after revision 13 July 1999; accepted 13 July 1999 相似文献
5.
The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid
cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 μM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase.
Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 μM of
either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder
was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of
polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug
treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity
against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.
Received 17 January 2002; received after revision 22 February 2002; accepted 22 February 2002 相似文献
6.
The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation 总被引:5,自引:1,他引:4
A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore
a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector
cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products,
resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and
loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory
pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response.
This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms
to circumvent destruction by the host.
Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005 相似文献
7.
Oxidative stress and hypoxia-like injury cause Alzheimer-type molecular abnormalities in central nervous system neurons 总被引:11,自引:0,他引:11
de la Monte SM Neely TR Cannon J Wands JR 《Cellular and molecular life sciences : CMLS》2000,57(10):1471-1481
Neuronal loss and neuritic/cytoskeletal lesions (synaptic disconnection and proliferation of dystrophic neurites) represent
major dementia-associated abnormalities in Alzheimer’s disease (AD). This study examined the role of oxidative stress as a
factor contributing to both the cell death and neuritic degeneration cascades in AD. Primary neuron cultures were treated
with H2O2 (9–90 μM) or desferrioxamine (2–25 μM) for 24 h and then analyzed for viability, mitochondrial mass, mitochondrial function,
and pro-apoptosis and sprouting gene expression. H2O2 treatment causes free-radical injury and desferrioxamine causes hypoxia-type injury without free radical generation. The
H2O2-treated cells exhibited sustained viability but neurite retraction, impaired mitochondrial function, increased levels of
the pro-apoptosis gene product CD95/Fas, reduced expression of N2J1-immunoreactive neuronal thread protein and synaptophysin,
and reduced distribution of mitochondria in neuritic processes. Desferrioxamine treatment resulted in dose-dependent neuronal
loss associated with impaired mitochondrial function, proliferation of neurites, and reduced expression of GAP-43, which has
a role in path-finding during neurite outgrowth. The results suggest that oxidative stress can cause neurodegeneration associated
with enhanced susceptibility to apoptosis due to activation of pro-apoptosis genes, neurite retraction (synaptic disconnection),
and impaired transport of mitochondria to cell processes where they are likely required for synaptic function. In contrast,
hypoxia-type injury causes neuronal loss with proliferation of neurites (sprouting), impaired mitochondrial function, and
reduced expression of molecules required to form and maintain synaptic connections. Since similar abnormalities occur in AD,
both oxidative stress and hypoxic injury can contribute to AD neurodegeneration.
Received 24 May 2000; received after revision 7 July 2000; accepted 27 July 2000 相似文献
8.
In type 1 diabetes (T1D), a break in central and peripheral tolerance results in antigen-specific T cells destroying insulin-producing,
pancreatic beta cells. Herein, we discuss the critical sub-population of dendritic cells responsible for mediating both the
cross-presentation of islet antigen to CD8+ T cells and the direct presentation of beta cell antigen to CD4+ T cells. These cells, termed merocytic dendritic cells (mcDC), are more numerous in non-obese diabetic (NOD), and antigen-loaded
mcDC rescue CD8+ T cells from peripheral anergy and deletion, and stimulate islet-reactive CD4+ T cells. When purified from the pancreatic lymph nodes of overtly diabetic NOD mice, mcDC can break peripheral T cell tolerance
to beta cell antigens in vivo and induce rapid onset T cell-mediated T1D in young NOD mouse. Thus, the mcDC subset appears
to represent the long-sought critical antigen-presenting cell responsible for breaking peripheral tolerance to beta cell antigen
in vivo. 相似文献
9.
Myelin sheaths: glycoproteins involved in their formation,maintenance and degeneration 总被引:8,自引:0,他引:8
Quarles RH 《Cellular and molecular life sciences : CMLS》2002,59(11):1851-1871
Myelin sheaths are formed around axons by extending, biochemically modifying and spiraling plasma membranes of Schwann cells
in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Because glycoproteins are
prominent components of plasma membranes, it is not surprising that they have important roles in the formation, maintenance
and degeneration of myelin sheaths. The emphasis in this review is on four integral membrane glycoproteins. Two of them, protein
zero (P0) and peripheral myelin protein-22 (PMP-22), are components of compact PNS myelin. The other two are preferentially
localized in membranes of sheaths that are distinct from compact myelin. One is the myelin-associated glycoprotein, which
is localized at the inside of sheaths where it functions in glia-axon interactions in both the PNS and CNS. The other is the
myelin-oligodendrocyte glycoprotein, which is preferentially localized on the outside of CNS myelin sheaths and appears to
be an important target antigen in autoimmune demyelinating diseases such as multiple sclerosis.
Received 8 April 2002; received after revision 13 May 2002; accepted 22 May 2002 相似文献
10.
Culture in low levels of oxygen enhances in vitro proliferation potential of satellite cells from old skeletal muscles 总被引:4,自引:0,他引:4
Chakravarthy MV Spangenburg EE Booth FW 《Cellular and molecular life sciences : CMLS》2001,58(8):1150-1158
The proliferation ability of satellite cells (considered the 'stem cells' of mature myofibers) declines with increasing age
when cultured under standard cell culture conditions of 21% oxygen. However, actual oxygen levels in the intact myofiber in
vivo are an order of magnitude lower. No studies to date have addressed the issue of whether culturing satellite cells from
old muscles under more 'physiologic' conditions would enhance their proliferation and/or differentiation ability. Therefore,
we analyzed satellite cells derived from 31-month-old rats in standard cultures with 21% O2 and in lowered (∼3%) O2. Under the lowered O2 conditions, we noted a remarkable increase in the percentage of large-sized colonies, activation of cell cycle progression
factors, phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27Kip1. These data suggest that lower O2 levels provide a milieu that stimulates proliferation by allowing continued cell cycle progression, to result ultimately
in the enhanced in vitro replicative life span of the old satellite cells. Such a method therefore provides an improved means
for the ex vivo generation of progenitor satellite cell populations for potential therapeutic stem cell transplantation.
Received 20 April 2001; received after revision 28 May 2001; accepted 31 May 2001 相似文献
11.
Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells 总被引:3,自引:0,他引:3
Shafqat J Juntti-Berggren L Zhong Z Ekberg K Köhler M Berggren PO Johansson J Wahren J Jörnvall H 《Cellular and molecular life sciences : CMLS》2002,59(7):1185-1189
Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide
and related molecules on the intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide
(positions 27–31, EGSLQ), but not the des (27–31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in
[Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca2+]i response, and those with Ala at positions 2–5 induce responses with different amplitudes. These results define a species
cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells
with pertussis toxin abolishes the effect on [Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and
activation of Na+,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.
Received 13 May 2002; accepted 16 May 2002 相似文献
12.
The role of the proteasome in the generation of MHC class I ligands and immune responses 总被引:2,自引:2,他引:0
The ubiquitin–proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major
histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition
differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory
cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome
activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of
thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class
I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions
of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses. 相似文献
13.
R. G. MacDonald R. H. McCusker D. J. Blackwood J. A. Vanderhoof J. H. Y. Park 《Cellular and molecular life sciences : CMLS》1998,54(2):158-166
To determine if intestinal stromal cells secrete diffusible factors such as insulin-like growth factors (IGFs) capable of
regulating epithelial cell growth in vitro, stromal cells were isolated by enzymatic digestion of rat intestine. Incorporation
of [3H]thymidine into DNA and [14C]leucine into protein of IEC-6 cells, a model intestinal epithelial cell line, was significantly increased (two- to threefold)
when the IEC-6 cells were co-cultured with stromal cells, relative to IEC-6 cells grown alone. Medium conditioned by stromal
cells stimulated DNA synthesis of IEC-6 cells in a dose-dependent manner. Analysis of the conditioned medium revealed that
intestinal stromal cells secreted IGF-I, but little IGF-II, in addition to an M
r 32,000 IGF-binding protein (IGFBP-2) and an IGFBP having M
r∼ 24,000. We conclude that rat intestinal stromal cells secrete one or more diffusible factors, which may include IGF-I and
IGFBPs, capable of stimulating proliferation of IEC-6 cells in vitro.
Received 25 August 1997; received after revision 7 November 1997; accepted 20 November 1997 相似文献
14.
Epithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti 总被引:2,自引:0,他引:2
Malgrange B Thiry M Van De Water TR Nguyen L Moonen G Lefebvre PP 《Cellular and molecular life sciences : CMLS》2002,59(10):1744-1757
The organ of Corti is a complex structure containing a single row of inner hair cells (IHCs) and three rows of outer hair
cells (OHCs), supported respectively by one row of inner phalangeal cells and three rows of Deiters' cells. When fetal rat
organ of Corti explants are cultured, supernumerary OHCs and supernumerary Deiters' cells are produced, without any additional
cell proliferation. Analysis of semi- and ultrathin sections revealed that supernumerary OHCs are produced at the distal edge
of the organ of Corti. Quantitative analysis of cell types present in the organ of Corti demonstrates that when the number
of OHCs increases: (i) the total number of cells remains constant; (ii) the number of Deiters' cells increases; (iii) the
number of tectal cells decreases and of Hensen's cells decreases. Using specific HC markers, i.e. jagged2 (Jag2) and Math1,
we showed that in addition to existing OHCs, supernumerary OHCs, tectal cells and Hensen's cells expressed these markers in
embryonic day 19 organ of Corti explants after 5 days in vitro. The results of this study suggest that Hensen's cells retain
the capacity to differentiate into either tectal cells, which differentiate into OHCs, or into undertectal cells which differentiate
into Deiters' cells.
Received 15 May 2002; received after revision 18 July 2002; accepted 7 August 2002
RID="*"
ID="*"Corresponding author. 相似文献
15.
Immune responses to DNA vaccines 总被引:16,自引:0,他引:16
DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promoter, have been shown to induce
protective immune responses to a number of pathogens, including viruses, bacteria and parasites. They have also displayed
efficacy in treatment or prevention of cancer, allergic diseases and autoimmunity. Immunologically, DNA vaccines induce a
full spectrum of immune responses that include cytolytic T cells, T helper cells and antibodies. The immune response to DNA
vaccines can be enhanced by genetic engineering of the antigen to facilitate its presentation to B and T cells. Furthermore,
the immune response can be modulated by genetic adjuvants in the form of vectors expressing biologically active determinants
or by more traditional adjuvants that facilitate uptake of DNA into cells. The ease of genetic manipulation of DNA vaccines
invites their use not only as vaccines but also as research tools for immunologists and microbiologists.
Received 26 October 1998; received after revision 3 December 1998; accepted 3 December 1998 相似文献
16.
Faust M Günther J Morgenstern E Montenarh M Götz C 《Cellular and molecular life sciences : CMLS》2002,59(12):2155-2164
The protein kinase CK2 holoenzyme is composed of two regulatory β subunits and two catalytic α or α' subunits. Although experimental
evidence for involvement of the enzyme in the regulation of cell proliferation is accumulating, the exact mechanism of its
action is still unclear. The subcellular localization of the enzyme may be a key to its function. We have recently shown that
the CK2 holoenzyme is tightly associated with the Golgi complex and the endoplasmic reticulum. Centrosomes, which organize
spindle formation during the cell cycle and microtubule cytoskeleton formation and, thereby, the location and orientation
of different organelles in the cell, are in close vicinity to the Golgi complex. Because several kinases and phosphatases
have been described to regulate the functions of the centrosome, we analysed the association of CK2 with these organelles.
Using biochemical cell fractionation and coimmunoprecipitation, we never found the holoenzyme but only the catalytic asubunits
associated with the centrosome. These data were confirmed by immunoelectron microscopy. Thus, the present data point to a
particular role of the catalytic α and α' subunit of protein kinase CK2, which may be different from their roles in the holoenzyme.
Received 2 August 2002; received after revision 2 October 2002; accepted 22 October 2002
RID="*"
ID="*"Corresponding author. 相似文献
17.
Wesch D Peters C Oberg HH Pietschmann K Kabelitz D 《Cellular and molecular life sciences : CMLS》2011,68(14):2357-2370
Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules
derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to
subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several
T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the
recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T
cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast
to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine
production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via
TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands
indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human
tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated
signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly
or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity
of γδ T cells. 相似文献
18.
Joyce S 《Cellular and molecular life sciences : CMLS》2001,58(3):442-469
Cellular and humoral immune mechanisms recruited to defend the host from infectious agents depend upon the early immune events
triggered by antigen. The cytokine milieu within which the immune response matures is the most important of many factors that
govern the nature of the immune response. Natural T cells, whose function is controlled by CD1d molecules, are an early source
of cytokines that can bestow type 1 or type 2 differentiative potential upon helper T lymphocytes. This review attempts to
illuminate the glycolipid antigen presentation properties of CD1d, how CD1d controls the function of natural T cells and how
CD1d and natural T cells interact to jump start the immune system. CD1d is postulated to function as a sensor, sensing alterations
in cellular lipid content by virtue of its affinity for such ligands. The presentation of a neo-self glycolipid, presumably
by infectious assault of antigen-presenting cells, activates natural T cells, which promptly release pro-inflammatory and
anti-inflammatory cytokines and jumpstart the immune system.
Received 10 July 2000; received after revision 16 October 2000, accepted 16 November 2000 相似文献
19.
Naïve CD4+ T cells undergo massive cell proliferation upon encountering their cognate ligand. This proliferation depends upon appropriate cues from the antigen-presenting cells that have processed the antigen and present the peptide to the T cells, and requires the establishment of a cytokine environment that can support such proliferation. Expansion of antigen-specific CD4+ T cells needs to be coupled with differentiation into one of several effector/regulatory phenotypes if the priming event is to result in cells that can initially act to control the particular pathogen that elicited the response, and later to serve as memory cells to insure an appropriate response upon reintroduction of the pathogen. Here, we discuss the initiation of T helper lineage commitment, the positive feedback regulation by the cytokine environment to enhance and stabilize the differentiation into distinct T helper subsets, and the biological significance of CD4+ T cell plasticity and long-term CD4+ T cell memory. 相似文献
20.
Immunomodulatory properties of cystatins 总被引:8,自引:0,他引:8
Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. Because these cysteine proteases exist in
all living organisms and because they are involved in various biological and pathological processes, the control of these
protease functions by cystatins is of cardinal importance. Cystatins are found in mammals but cystatin-like molecules are
also present in mammals and parasites. In the immune system, cystatins modulate cathepsin activities and antigen presentation.
They also induce tumor necrosis factor α and interleukin 10 synthesis, and they stimulate nitric oxide production by interferon
γ-activated murine macrophages. In turn, nitric oxide has inhibitory activity on cysteine proteases, especially those from
parasitic protozoa. Cystatins isolated from parasitic nematodes also have immunomodulatory activities that are distinguishable
from those induced by lipopolysacharide-like molecules from endosymbiotic bacteria. On the whole, cystatins and cystatin-like
molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of
this property, leading to practical applications in immunotherapy.
Received 11 April 2002; accepted 18 April 2002
RID="*"
ID="*"Corresponding author. 相似文献