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Biomedical subjects

Feng Gao

Publications and source records attributed to Feng Gao.

At least 253 records · Page 14Linked to original sources
PubMed2003

[Anti-apoptotic effect of insulin in myocardial ischemia-reperfusion and its principal signaling pathway].

OBJECTIVE: To investigate the signaling pathway involved in the insulin-elicited anti-apoptotic effect during myocardial ischemia and reperfusion (MI/R) in vivo. METHODS: Male Sprague-Dawley rats were anesthetized and subjected to 30 min of myocardial ischemia followed by 4h-reperfusion. Rats were randomly treated with intravenous infusion of saline (vehicle, 4 ml.kg(-1).h(-1)), insulin (60 U/L), or insulin + wortmannin 5 min before reperfusion and continuing throughout the 4h-reperfusion period. Cardiac myocyte apoptosis was determined both qualitatively and quantitatively by DNA laddering and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) methods. Myocardial nitric oxide (NO) was measured by using NO-specific chemiluminescence detector. Activations of Akt and p38 mitogen-activated protein kinase (MAPK) were determined by kinase activity assays using corresponding kinase activity assay kits (Cell Signaling). RESULTS: In the vehicle-treated rats, MI/R caused significant cardiac myocyte apoptotic death. Treatment with insulin produced a significant anti-apoptotic effect as evidenced by a marked reduction of apoptotic index [(8.0 +/- 2.9)% vs. (19.3 +/- 4.6)% of vehicle, P < 0.01] and decreased formation of myocardial DNA fragmentation. In addition, insulin treatment produced 2.7-fold increase (P < 0.01) of myocardial Akt activity and 28% increase of myocardial NO production (P < 0.05), while p38 MAPK activity changed insignificantly as compared with that of vehicle (P > 0.05). Both insulin-induced Akt activation and anti-apoptotic effect could be abrogated by wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor. CONCLUSION: In vivo treatment with insulin at the initial of reperfusion significantly reduced postischemic apoptotic death via the PI3-kinase-Akt signaling pathway. Akt, but not p38 MAPK, activation plays a key role in the insulin-induced anti-apoptotic effect in MI/R.

Animals↗
PubMed2003

[Endovascular stent-graft repair of aortic arch aneurysms: report of 46 patients].

OBJECTIVE: To evaluate the basic procedure of endovascular stent-graft repair in the treatment of aortic arch aneurysm. METHODS: >From March 2000-February 2002, a total of 46 patients with aortic arch aneurysms were treated with the custom-made endovascular stent-graft. Of them, twenty-three patients (50%) had aneurysms at the middle of the arch, 22 patients (48%) had aneurysms at the arch-descending aorta, and 1 patient (2%) had aneurysm at the descending thoracic aorta. The diameter of all stents was 0.15 - 0.25 times larger than that of the aorta proximal to the entry tear of dissection or the opening of aneurysm. The diameter of the proximal end of the stents was ranged from 34 - 38 mm. The length of stents ranged from 90 - 120 mm. The stent was made of shape memory nitinol. RESULTS: The stent was delivered successfully in 45 patients (98%). None of the patients had any access-related complications. Either the primary entry tear of aortic dissection or the inlet of aneurysm was occluded in 43 patients (96%), with an early endoleak in 2 patients (4%). All truth lumen of the dissection recovered to normal. Of the patients in acute period, 1 was referred to surgical repair and 2 died. Follow-up for 1 month to 23 months, showed late endoleak in 3 patients (7%). Forty-three patients restored normal life. CONCLUSIONS: Endovascular stent-graft could be applied in the repair of aortic arch aneurysm. Further studies are needed to to assess the long-term efficacy of this method.

Adult↗
PubMed2003

[Mitochondrial DNA mutations in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome].

OBJECTIVE: Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) belong to neurological diseases caused by a defect in the energy-producing system of mitochondria, and are known to be associated with a deletion in the mitochondrial genome. This study was aimed to understand with greater clearness the characteristics of mitochondrial DNA (mtDNA) mutations in 11 Chinese patients with CPEO (7 cases) or KSS (4 cases). METHODS: Densitometry of the bands on Southern blot, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing were performed to search large scale deletions and A3243G point mutation in patients' muscle mtDNA. RESULTS: Large deletions in mtDNA were detected in 2 CPEO and 3 KSS patients, the size of deletion ranged from 3.0 kb to 8.0 kb. Moreover, mtDNA A3243G point mutation was identified in 1 KSS patient. The proportion of mutant mtDNA was 37.6%-87.0%. Direct sequencing of the PCR products revealed 5 novel large deletions not reported by others. CONCLUSION: The findings in this study being consistent with the reports by others, large scale deletions of mtDNA are frequently found in Chinese patients with KSS and CPEO. mtDNA A3243G mutation may also exist in some patients with KSS and CPEO.

Adolescent↗
PubMed2003

[Coronary artery bypass graft for patients with ascending aorta atherosclerosis].

OBJECTIVE: The increasing number of aged patients with severe ascending aorta atherosclerosis who are undergoing coronary artery bypass graft (CABG) present high risk for ascending aortic cannulation, cross-clamping or partial occluding and proximal anastomosis. We reviewed the surgical experience in 22 patients of CABG with ascending aorta atherosclerosis and tried to find the way to minimize the complications. METHODS: Twenty-two patients with severe atherosclerotic and calcified ascending aorta underwent CABG in our hospital. Thirteen of them received CABG on beating heart. Nine patients had their CABG with extracorporeal circulation. With deep hypothermia, we reduced the flow rate and intermittently arrested the circulation for the proximal anastomosis on ascending aorta in 5 patients with neither cross-clamping nor partial occluding. The sequential grafts and "Y" type anastomosis between reversed saphenous venous grafts were employed. RESULTS: Twenty of the patients survived after surgery. One died of inhalation pneumonia in two weeks after surgery. Another died of right hemothorax in ten days after surgery. The complications include: pneumonia 4 patients (18%), angina 2 patients (9%), ventricular fibrillation 1 patients (5%), post-CABG myocardium infarction 1 case (5%) and hemothorax 1 case (5%). There is no neurologic complications or aortic dissection after CABG. CONCLUSION: CABG on beating heart with pedicel arterial grafts is the best approach to performing the surgery without touching the diseased ascending aorta. Ventricular fibrillation under mild hypothermia cardiopulmonary bypass and left ventricular suction were employed for quiet and bloodless field while distal anastomosis had no cross-clamping the ascending aorta. Also deep hypothermia and intermittently circulatory arrest offer quiet and bloodless field for the proximal anastomosis on ascending aorta without cross-clamping or partial-occluding. Distal sequential anastomosis and proximal "Y" type anastomosis are the effective approach to minimizing the proximal anastomosis on the ascending aorta.

Aged↗
PubMed2003

[The biological activity of MHC classII transactivator ribonuclease P: a novel approach for hepatic transplantation rejection].

OBJECTIVE: This paper studied the effect of RNaseP against CIITA on repressing class II MHC (MHCII) expression. METHODS: It was constructed that M1-RNA with guide sequences (GS), recognizing the 629 site of CIITA (M1-629-GS), by PCR from pTK117 plasmid, then was cloned into psNAV (psNAV-M1-629-GS). CIITA target gene was obtained from Raji cell by RT-PCR, and then inserted into pGEM-7zf (+) (pGEM-800). psNAV-M1-629-GS and pGEM-800 were transcribed and then mixed up and incubated in vitro. Stable transfectants of hepatocyte with psNAV-M1-629-GS by nanometer were tested for MHCII induction by recombinant human interferon-gamma (IFN-gamma). mRNA abundance of CIITA was measured by RT-PCR. RESULTS: It showed that M1-629-GS could exclusively cleave pGEM-800 that formed a base pair with the GS. When induced with IFN-gamma, the expression of HLA-DR, -DP, -DQ on psNAV-M1-629-GS+ hepatocyte was (1.01+/-0.51)%, (4.37+/-1.28)%, (1.98+/-0.42)% respectively, was down-modulated 90.65%, 89.11% and 65.32% compared with control, while the mRNA content of CIITA reduced significantly (P<0.01). CONCLUSION: M1-629-GS could effectively repress MHCII expressing through cleaving CIITA mRNA. These results provided insight into the future application of it as a new nucleic acid drug against the rejection of hepatic transplantation.

Graft Rejection↗
PubMed2003

[Inhibition effect of CIITA anti-sense cDNA on the expression of MHCII molecules of Hela cells].

OBJECTIVE: To investigate the inhibiting effect of classII major histocompatibility complex transactivator (CIITA) anti-sense cDNA on MHCII molecules expression. METHODS: CIITA antisense cDNAs (arII1, arII2 and arII3) were obtained from Raji cell by RT-PCR, and then inserted into the pcDNA3.1B plasmid. The stable transfectants of Hela cell were tested for CIITA protein by immunohistochemistry, and classic MHCII molecules (HLA-DR, -DP, -DQ) induction through recombinant human IFN-gamma by flow cytometry. mRNAs of CIITA, invariant chain and classic MHCII molecules were detected by RT-PCR. RESULTS: The effect of arII2 was the best. When induced with IFN-gamma, the expression of CIITA protein was inhibited by 87.23%, and that of HLA-DR, -DP and -DQ was almost totally inhibited on arII2 positive Hela cells. The mRNA contents of CIITA, HLA-DR, -DP, -DQ and invariant chain were decreased significantly (P < 0.05). CONCLUSIONS: arII2 inhibits CIITA and thus the family of MHCIImolecules regulated by CIITA, therefore, it provides a novel approach to graft versus host disease study in hematopoietic stem cell transplantation.

DNA, Antisense↗
PubMed2002

Correlation between methotrexate-induced intestinal damage and decrease in polyamine content.

A synthetic analog of prostaglandin E(1), OP-1206 [17S, 20-dimethyl-trans-Delta(2)-prostaglandin E(1)] protects the small intestine from the methotrexate (MTX)-induced damage. The purpose of this study is to evaluate the protective effect of OP-1206 on the methotrexate-induced small intestinal damage in rats from the biochemical point of view. MTX (15 mg/kg body weight) was orally administered to rats once daily for 5 days. OP-1206 (0.5 microg/kg body weight) was orally administered to rats twice a day for 5 days, and on the 6th day biochemical components in the jejunal mucosa of the treated rats were determined. The contents of DNA, RNA, proteins and polyamines (spermine and spermidine) in the jejunal mucosa of rats were markedly decreased by the MTX treatment. The coadministration of OP-1206 with MTX prevented such decreases caused by the MTX treatment. The MTX treatment decreased the incorporation of 3H-thymidine into DNA in the jejunal mucosa, while the coadministration of OP-1206 with MTX prevented it. These results indicated that OP-1206 could protect the intestinal mucosa against the biochemical effects of MTX through a trophic action on intestinal villi. Further, it should be noted that polyamines may possibly play an important role of modulation action on intestinal mucosa.

Administration, Oral↗
PubMed2002

Crystallization and preliminary crystallographic analysis of a partial extracellular fragment of a sperm membrane protein YWK-II/APPH related to the Alzheimer betaA4-amyloid precursor protein.

Crystals of a partial extracellular fragment of a human sperm membrane protein YWK-II/APPH have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.8 A resolution at 100 K using Cu K(alpha) radiation. The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.009, b = 67.387, c = 149.241 A, alpha = beta = gamma = 90 degrees. The presence of two molecules per asymmetric unit gives a crystal Volume per protein mass (V(M)) of 3.51 A(3) Da(-1) and a solvent content of 64.6% by Volume. A full set of X-ray diffraction data were collected to 2.8 A resolution from the native crystal.

Amino Acid Sequence↗
PubMed2002

Semi-three-dimensional algorithm for time-resolved diffuse optical tomography by use of the generalized pulse spectrum technique.

Although a foil three-dimensional (3-D) reconstruction with both 3-D forward and inverse models provide, the optimal solution for diffuse optical tomography (DOT), because of the 3-D nature of photon diffusion in tissue, it is computationally costly for both memory requirement and execution time in a conventional computing environment. Thus in practice there is motivation to develop an image reconstruction algorithm with dimensional reduction based on some modeling approximations. Here we have implemented a semi-3-D modified generalized pulse spectrum technique for time-resolved DOT, where a two-dimensional (2-D) distribution of optical properties is approximately assumed, while we retain 3-D distribution of photon migration in tissue. We have validated the proposed algorithm by reconstructing 3-D structural test objects from both numerically simulated and experimental date. We demonstrate our algorithm by comparing it with the calibrated 2-D reconstruction that is in widespread use as a shortcut to 3-D imaging and proving that the semi-3-D algorithm outperforms the calibrated 2-D algorithm.

Algorithms↗
PubMed2002

Expression, crystallization and preliminary X-ray studies of the recombinant PTB domain of human dok-5 protein.

The human dok-5 PTB domain fusion protein has been overexpressed in Escherichia coli and crystallized in a form suitable for X-ray crystallographic study. Crystals were obtained by the vapour-diffusion method. The crystal has unit-cell parameters a = b = 75.9, c = 108.0 A, alpha = beta = 90, gamma = 120 degrees and belongs to space group P3(2)21. Diffraction data were collected to 2.8 A resolution in-house. Furthermore, a selenomethionine (SeMet) derivative of dok-5 PTB domain fusion protein was overexpressed using the same expression system and was purified in a reductive environment. The derivative crystals were obtained under similar conditions. Subsequently, three different wavelength data sets were collected to 2.3 A resolution from the derivative crystal at the Advanced Photon Source, Argonne National Laboratory.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Allograft rejection by primed/memory CD8+ T cells is CD154 blockade resistant: therapeutic implications for sensitized transplant recipients.

We have shown that CD8(+) CTLs are the key mediators of accelerated rejection, and that CD8(+) T cells represent the prime targets of CD154 blockade in sensitized mouse recipients of cardiac allografts. However, the current protocols require CD154 blockade at the time of sensitization, whereas delayed treatment fails to affect graft rejection in sensitized recipients. To elucidate the mechanisms of costimulation blockade-resistant rejection and to improve the efficacy of CD154-targeted therapy, we found that alloreactive CD8(+) T cells were activated despite the CD154 blockade in sensitized hosts. Comparative CD8 T cell activation study in naive vs primed hosts has shown that although both naive and primed/memory CD8(+) T cells relied on the CD28 costimulation for their activation, only naive, not primed/memory, CD8(+) T cells depend on CD154 signaling to differentiate into CTL effector cells. Adjunctive therapy was designed accordingly to deplete primed/memory CD8(+) T cells before the CD154 blockade. Indeed, unlike anti-CD154 monotherapy, transient depletion of CD8(+) T cells around the time of cardiac engraftment significantly improved the efficacy of delayed CD154 blockade in sensitized hosts. Hence, this report provides evidence for 1) differential requirement of CD154 costimulation signals for naive vs primed/memory CD8(+) T cells, and 2) successful treatment of clinically relevant sensitized recipients to achieve stable long term graft acceptance.

Animals↗
PubMed2002

Analysis of partial pol and env sequences indicates a high prevalence of HIV type 1 recombinant strains circulating in Gabon.

Forty-one HIV-1 strains from Gabonese patients were studied according to the following strategy: nested polymerase chain reaction were performed to obtain an approximately 1,100-bp fragment containing the protease gene and the 5' half of the reverse transcriptase gene. Additional amplifications were carried out to obtain an approximately 700-bp fragment encompassing the C2V3 env gene. Fragments of 600 to 1,200 bp in the gag gene overlapping the pol sequences were used for the study of recombination patterns. Phylogenetic analyses of the different fragments were used to investigate HIV-1 diversity in Gabon. Thirty-one strains were sequenced in the env and pol genes and phylogenetic analyses classified them as subtype A (n = 2), D (n = 4), G (n = 1), H (n = 1), CRF02 (n = 8), and CRF MAL-like (n = 6); in addition, there were 6 unique recombinant forms and 1 unclassified strain, and in 2 cases pol/env sequences classified strains as subtype D whereas gag phylogeny classified them as subtype A. In 10 cases only 1 fragment was available: 4 env (2 subtype D, 1 subtype H, and 1 subtype U) and 6 pol (1 subtype A, 1 subtype C, 2 subtype G, and 2 subtype U). Minor mutations associated with viral resistance to antiretroviral drugs were observed in more than 80% of analyzed strains. Our study confirms the extensive HIV-1 diversity found in Central Africa, with more than 70% of strains from Gabon exhibiting discordant clustering in pol and env genomic regions and less than 60% concordance between sequencing and heteroduplex mobility assay genotyping. These findings highlight the fact that Central Africa represents the epicenter for the origin of HIV-1. The strategy of sequencing pol in association with env has proved to be useful for analysis of the recombinant strains. The main advantage of this approach is that it also allows for evaluation of genotypic susceptibility to antiretroviral drugs without the need for supplementary analyses.

Amino Acid Sequence↗
PubMed2002

Heme oxygenase 1 mediates the immunomodulatory and antiapoptotic effects of interleukin 13 gene therapy in vivo and in vitro.

This study analyzes mechanisms by which interleukin 13 (IL-13) affects "infectious tolerance" in rat recipients of cardiac allografts, with emphasis on interactions between intragraft Ad-IL-13 gene transfer and systemic infusion of regulatory cells. Although exogenous viral IL-13 was modestly effective on its own, adjunctive Ad-IL-13 gene therapy and adoptive transfer of suboptimal dose of regulatory T cells exerted synergistic effects, as evidenced by long-term cardiac allograft survival in test recipients. Local IL-13 induction (determined by enzyme-linked immunosorbent assay and immunohistology) diminished intragraft apoptosis, and upregulated antiapoptotic A20 and antioxidant heme oxygenase 1 (HO-1). Ad-IL-13 plus regulatory cells synergistically diminished the frequency of cells positive by TUNEL (TdT [terminal deoxynucleotidyltransferase]-mediated dUTP nick-end labeling) assay, and enhanced cytoprotective gene expression. These findings correlated with in vitro studies in which Ad-IL-13 decreased tumor necrosis factor alpha (TNF-alpha)-mediated cytotoxicity, conferred resistance to apoptosis, and increased HO-1/A20 expression in human umbilical vein endothelial cell (HUVEC) cultures. However, inhibition of HO-1 after treatment with tin protoporphyrin reversed the immunomodulatory/antiapoptotic effects of Ad-IL-13 both in vivo (infectious transplantation tolerance), and in vitro (HUVECs). Thus, by decreasing apoptosis/TNF-alpha-mediated cytotoxicity, and by facilitating induction of antiapoptotic/antioxidant molecules in HUVECs, this study documents the cytoprotective function of Ad-IL-13 in vitro, and points toward in vivo synergy between Ad-IL-13 and regulatory cells in the infectious transplantation tolerance pathway. Results of HO-1 neutralization studies suggest that HO-1 represents one of the putative IL-13 downstream effectors.

Animals↗
PubMed2002

NF-kappaB mediates IL-1beta-induced synthesis/release of alpha2-macroglobulin in a human glial cell line.

Increasingly, inflammatory responses in localized areas of brain parenchyma in response to the extracellular deposition of the Abeta peptides are thought to play a causative role in Alzheimer's disease (AD) progression. Anti-inflammatory agents, in particular non-steroid anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, have been shown to be associated with a delayed onset or slowed rate of disease progression in several epidemiological studies. Activation of glial cells and the subsequent expression of a number of proteins including alpha(2)-macroglobulin (alpha(2)M) are associated with the induction of brain tissue inflammation. Additionally cytokines, such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) are co-localized to senile plaques, a neuropathological hallmark of AD. Alpha(2)M binds various cytokines, including IL-1beta, as well as Abeta. In this study, we demonstrate that IL-1beta induces alpha(2)M synthesis/release from a human astroglial cell line (U373) via the activation of the nuclear transcription factor NF-kappaB. Our data suggest that attenuation of IL-1beta-induced alpha(2)M synthesis/release by blocking NF-kappaB activation may potentially be 'protective' against the development of late-onset AD.

Alzheimer Disease↗
PubMed2002

CD154-CD40 T-cell costimulation pathway is required in the mechanism of hepatic ischemia/reperfusion injury, and its blockade facilitates and depends on heme oxygenase-1 mediated cytoprotection.

BACKGROUND: Ischemia/reperfusion (I/R) injury remains an important clinical problem that affects both early and later allograft outcome. This study was designed to analyze the role of T cells and CD154-CD40 T- cell costimulation pathway in a mouse liver I/R model. METHODS AND RESULTS: Ninety minutes of warm ischemia followed by 4 h of reperfusion in wild-type (WT) mice resulted in a significant hepatic damage, as assessed by liver function (serum alanine aminotransferase [sALT] levels), local neutrophil accumulation (myeloperoxidase activity), and histology (Suzuki's score). In contrast, T-cell deficiency (in T-cell deficient [nu/nu] mice), disruption of the CD154 signaling (in knockout [KO] mice), or its blockade in WT recipients (after MR1 monoclonal antibody [mAb] treatment), virtually prevented hepatic I/R insult. Unlike CD154-deficient T cells, adoptive transfer of WT spleen cells fully restored hepatic I/R injury in nu/nu mice. Finally, the improved hepatic function in CD154 KO recipients, WT mice treated with CD154 mAb, or nu/nu mice infused with CD154-deficient cells resulted in consistently enhanced expression of heme oxygenase-1 (HO-1), a heat-shock protein with cytoprotective functions. CONCLUSION: This study confirms the importance of T cells, and documents for the first time the role of CD154 costimulation signals in the mechanism of hepatic I/R injury. We also show that CD154 blockade-mediated cytoprotection results and depends on HO-1 overexpression. Our data provide the rationale for human trials to target CD154-CD40 costimulation in hepatic I/R injury, particularly in the transplant patient.

Adoptive Transfer↗
PubMed2002

Precambrian animal life: probable developmental and adult cnidarian forms from Southwest China.

The evolutionary divergence of cnidarian and bilaterian lineages from their remote metazoan ancestor occurred at an unknown depth in time before the Cambrian, since crown group representatives of each are found in Lower Cambrian fossil assemblages. We report here a variety of putative embryonic, larval, and adult microfossils deriving from Precambrian phosphorite deposits of Southwest China, which may predate the Cambrian radiation by 25-45 million years. These are most probably of cnidarian affinity. Large numbers of fossilized early planula-like larvae were observed under the microscope in sections. Though several forms are represented, the majority display remarkable conformity, which is inconsistent with the alternative that they are artifactual mineral inclusions. Some of these fossils are preserved in such high resolution that individual cells can be discerned. We confirm in detail an earlier report of the presence in the same deposits of tabulates, an extinct crown group anthozoan form. Other sections reveal structures that most closely resemble sections of basal modern corals. A large number of fossils similar to modern hydrozoan gastrulae were also observed. These again displayed great morphological consistency. Though only a single example is available, a microscopic animal remarkably similar to a modern adult hydrozoan is also presented. Taken together, the new observations reported in this paper indicate the existence of a diverse and already differentiated cnidarian fauna, long before the Cambrian evolutionary event. It follows that at least stem group bilaterians must also have been present at this time.

Animals↗
PubMed2002

The CD154-CD40 T cell costimulation pathway is required for host sensitization of CD8(+) T cells by skin grafts via direct antigen presentation.

Although the CD154-CD40 T cell costimulation pathway has been shown to mediate alloimmune responses in normal recipients, little is known about its role in sensitized hosts. In this work, by using novel models of cardiac allograft rejection in skin-sensitized CD154- and CD40-deficient mice, we reaffirm the key role of CD154-CD40 signaling in host sensitization to alloantigen in vivo. First, we identified CD8(+) T cells as principal effectors in executing accelerated rejection in our model. Disruption of CD154-CD40 signaling in recipients at the T cell side (CD154-deficient) but not at the APC side (CD40-deficient) abrogated accelerated (<2 days) rejection and resulted in long-term (>100 days) graft survival. This suggests that the CD154-dependent mechanism in host CD8(+) T cell sensitization operates via the direct Ag presentation. Then, in comparative studies of alloimmune responses in CD154-deficient and wild-type recipients, we showed that, although alloreactive B cell responses were inhibited, alloreactive T cell responses were down-regulated selectively in the CD8(+) T cell compartment, leaving CD4(+) T cells largely unaffected. This unique alteration in host alloreactivity, seen not only in peripheral lymphocytes but also in allograft infiltrate, may represent the key mechanism by which disruption of CD154-CD40 signaling prevents sensitization to alloantigen in vivo and leads to long-term allograft survival.

Animals↗