Plasma concentrations of transforming growth factor beta 1 in non-progressive HIV-1 infection correlates with markers of disease progression

The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF β 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n = 14) and progressive infection (n = 47), plasma levels of active TGF β 1, INF-γ, TNF-α, IL-10, IL-1β, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n = 12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF β 1 and IL-10 were significantly decreased while IL-1β, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF β 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1β, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these findings may have implications for systemic cytokine-based therapies in HIV-1 infection.     

CD4+CD25+FoxP3+ 调节性T 细胞与黑龙江省HIV/AIDS 患者病情 相关性的研究

目的:比较黑龙江省HIV/AIDS患者与健康对照者(healthy controls,HCs)外周血CD4+CD25+FoxP3+调节性T细胞数量、免疫抑制功能的变化,探讨CD4+CD25+FoxP3+调节性T细胞在HIV/AIDS感染过程中的作用。方法:采用流式细胞仪检测21例HIV/AIDS患者及20例健康对照组的外周血CD4+CD25+FoxP3+调节性T细胞数量的百分比及绝对数量;采用共同培养方法检测HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞免疫抑制功能的变化;实时荧光定量聚合酶链反应(RT-FQ-PCR)检测HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞中FoxP3mRNA的表达。结果:黑龙江省HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞比率明显高于HCs(P<0.01),而CD4+CD25+FoxP3+调节性T细胞的绝对计数显著下降,且与CD4+T细胞绝对计数成反比;混合淋巴细胞共同培养结果显示,HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞的抑制功能无明显变化;HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞的FoxP3 mRNA相对表达量无显著变化。结论:黑龙江省HIV/AIDS患者CD4+CD25+FoxP3+调节性T细胞的数量变化与病情相关。     

外周全血中与老化相关的DNA甲基化标记的来源

机体老化与癌症、神经退行性疾病等许多复杂疾病相关。目前,研究者已在外周全血中识别了大量的与老化相关的DNA甲基化标记,这些标记可能反映外周血白细胞在机体老化过程中发生的变化,也可能反映外周血中与年龄相关的细胞构成比例的变化。文章利用3组正常个体外周全血DNA甲基化谱,采用Spearman秩相关分析识别了与老化相关的CpG甲基化位点(age-related DNA methylation CpG sites, arCpGs)并评价了其可重复性;利用去卷积算法估计了各外周血样本中髓性和淋巴性细胞的比例并分析了其与年龄的相关性;比较了在外周全血、CD4+T细胞和CD14+单核细胞中识别的arCpGs的一致性。结果显示,在独立外周全血数据中识别的arCpGs具有显著的可重复性(超几何检验,P=1.65×10^-11)。外周血髓性和淋巴性细胞的比例分别与年龄显著正、负相关(Spearman秩相关检验,P<0.05,r≤0.22),它们间DNA甲基化水平差异较大的CpG位点倾向于在外周全血中被识别为arCpGs。在CD4+T细胞中识别的arCpGs与在外周全血中识别的arCpGs显著交叠(超几何检验,P=6.14×10^-12),且99.1%的交叠位点在CD4+T细胞及外周全血中的DNA甲基化水平与年龄的正、负相关性一致。尽管在CD14+单核细胞中识别的arCpGs与在外周全血中识别的arCpGs并不显著交叠,但是在交叠的51个arCpGs中,有90.1%的位点在CD14+单核细胞、外周全血以及CD4+T细胞中的DNA甲基化水平与年龄的正、负相关性一致,提示它们可能主要反映细胞间共同的改变。在外周全血中识别的arCpGs主要反映某些白细胞共同或特异的DNA甲基化改变,但是也有一部分反映外周血细胞比例构成的变化。     

非霍奇金淋巴瘤患者外周血中CD4+CD25+ 调节性T 细胞 亚群变化初探

目的:检测非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL)患者外周血中CD4+CD25+调节性T细胞(CD4+CD25+regulatoryT cell,Treg)的改变,探讨Treg与NHL的相关性。方法:病例组(n=60)为本院收治的初诊NHL患者,对照组(n=60)为本院健康体检者,用流式细胞技术联合标记CD4、CD25检测对照组及病例组化疗前、化疗后的外周血中CD4+CD25+调节性T细胞的分布特点。结果:(1)病例组化疗前外周血中CD4+细胞比例显著低于对照组(P<0.05),CD4+CD25+调节性T细胞比例显著高于对照组(P<0.05);(2)病例组化疗后,CD4+细胞比例明显高于化疗前(P<0.05),CD4+CD25+调节性T细胞比例明显低于化疗前(P<0.05);(3)病例组化疗后CD4+细胞比例与对照组无显著差异(P>0.05),而CD4+CD25+调节性T细胞比例显著高于对照组(P<0.05)。结论:非霍奇金淋巴瘤患者外周血中CD4+CD25+调节性T细胞比例升高,存在机体免疫抑制,化疗可降低CD4+CD25+调节性T细胞比例。     

Decreased regulatory T‐cells and CD4+/CD8+ ratio correlate with disease onset and progression in patients with generalized vitiligo

The aim of present study was to evaluate CD4⁺/CD8⁺ ratio and CD4⁺CD25^hiFoxP3⁺ Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4⁺/CD8⁺ ratio and Tregs in 82 patients and 50 controls. CD8⁺ T‐cell counts were significantly higher in GV patients as compared with controls (p = 0.003). Active GV patients showed higher CD8⁺ T‐cell counts compared with stable GV patients (p = 0.001). The CD4⁺/CD8⁺ ratio decreased significantly in patients as compared with controls (p = 0.001). Moreover, the ratio in active GV patients significantly lowered as compared with stable GV patients (p = 0.002). Significant decrease in Treg cell percentage and counts in GV patients was observed compared with controls (p = 0.009, p = 0.008) with significant reduction in FoxP3 expression (p = 0.024). Treg cell percentage and counts were significantly decreased in active GV patients compared with stable GV patients (p = 0.007, p = 0.002). Our results suggest that an imbalance of CD4⁺/CD8⁺ ratio and natural Tregs in frequency and function might be involved in the T‐cell mediated pathogenesis of GV and its progression.     

HIV-specific CD8+ T cell responses to HXB2 Gag and Nef peptide pools in Chinese HIV/AIDS patients

HXB2 is primarily used as a template strain in developing HIV vaccines in Europe and the US. However,it is not yet known whether the strain can induce strong HIV-specific CD8+ T cell responses in Chinese HIV/AIDS patients. In the present study,two groups of subjects were investigated:9 AIDS patients and 7 long-term nonprogressors (LTNPs). HIV-specific CD8+ T cell responses were examined in all patients through the ELISPOT assay. CD4+ T cell counts,CD8+ T cell counts,viral load and HIV subtype of each patien...     

口服卡介菌诱导免疫耐受的CD4+CD25+调节性T 细胞机制研究

目的:研究口服卡介菌诱导免疫耐受对CD4+CD25+调节性T细胞的影响。方法:采用口服MPB制备EAE大鼠模型,随机分为BCG组(0.5mg/kg)和EAE模型组(PBS),每组各15只,连续经口灌服给药14d,同时选取15只健康大鼠作为对照组。分别于免疫后15d、27d流式细胞术检测外周血、胸腺及脾脏中CD4+CD25+T淋巴细胞百分率,ELISA检测血清IL-6、TGF-β、IgE、IgG含量。结果:与EAE模型组相比,免疫后BCG组大鼠外周血、胸腺及脾脏中CD4+CD25+T淋巴细胞百分率增加,血清IL-6、TGF-β含量上升,血清IgE、IgG抗体水平下降。结论:口服BCG通过上调淋巴器官中CD4+CD25+T淋巴细胞比例,抑制效应性T细胞活性,发挥免疫耐受作用。     

Vascular-access-port implantation for serial blood sampling in conscious swine

A method to simplify serial venous blood sampling in miniature pigs was developed. Jugular vein Vascular-Access-Ports (VAP) were implanted in four animals. The mean functional lifetime of these ports was 37.7 +/- 23.0 (S.D.) days with a range of 17 to 77 days. The VAP allowed easy serial blood sampling and intravenous drug administration. Use of these ports in animals restrained in a sling was simple and effective and caused no undue stress to the animal over a 6 to 8 hour experiment. The VAPs were implanted easily and required minimal maintenance. Subcutaneous location of the entire apparatus allowed for group housing of the pigs and decreased the susceptibility of postoperative infection and/or damage. Provided that proper maintenance and careful aseptic sampling techniques are used, the VAP is a relatively easy, safe and reliable alternative to conventional methods of serial blood sampling in swine.     

Ability of CD8(+) T cell anti-feline immunodeficiency virus activity correlated with peripheral CD4(+) T cell counts and plasma viremia

In the host defense mechanism against feline immunodeficiency virus (FIV) infection, CD8(+) T cells specifically attack virus-infected cells and suppress the replication of the virus in a non-cytolytic manner by secreting soluble factors. In this study, we measured CD8(+) T cell anti-FIV activity in 30 FIV-infected cats. We investigated its relationship with the number of peripheral blood lymphocytes, particularly the CD4(+) T cell and CD8(+) T cell counts, and the relationship between anti-FIV activity and the number of T cells of CD8alpha(+)beta(lo) and CD8alpha(+)beta(-) phenotypes. A clearly significant correlation was observed between anti-FIV activity and the number of CD4(+) T cells. A weaker anti-FIV activity was associated with a greater decrease in the number of CD4(+) T cells. However, there was no significant correlation between anti-FIV activity and the number of B or CD8(+) T cells. Compared with SPF cats, FIV-infected cats had significantly higher CD8alpha(+)beta(lo) T cell and CD8alpha(+)beta(-) T cell counts, but, no significant correlation was observed between these cell counts and anti-FIV activity. This anti-FIV activity significantly correlated with plasma viremia, which was detected in cats with a weak anti-FIV activity. These results suggest that the anti-FIV activity of CD8(+) T cells plays an important role in plasma viremia and the maintenance of CD4(+) T cells in the body. It is unlikely that CD8alpha(+)beta(lo) or CD8alpha(+)beta(-) T cells appearing after FIV infection represent a phenotype of CD8(+) cells with anti-FIV activity.     

Identification of circulating CD90 CD73 cells in cirrhosis of liver

AIM:To identify circulating CD90 + CD73 + CD45 cells and evaluate their in vitro proliferating abilities.METHODS:Patients with cirrhosis(n=43),and healthy volunteers(n=40)were recruited to the study.Mononuclear cells were isolated and cultured from the peripheral blood of controls and cirrhosis patients.Fibroblast-like cells that appeared in cultures were analyzed for morphological features,enumerated by flow cytometry and confirmed by immunocytochemistry(ICC).Colony forming efficiency(CFE)of these cells was assessed and expressed as a percentage.RESULTS:In comparison to healthy volunteers,cells obtained from cirrhotic patients showed a significantincrease(P<0.001)in the percentage of CD90+CD73+ CD45 cells in culture.Cultured cells also showed 10 fold increases in CFE.Flow cytometry and ICC confirmed that the proliferating cells expressed CD90 + CD73 + in the cultures from cirrhosis patients.CONCLUSION:These results indicate the presence of circulating CD90 + CD73 + CD45 cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate.     

The α-test: rapid cell-free CD4 enumeration using whole saliva

There is an urgent need for affordable CD4 enumeration to monitor HIV disease. CD4 enumeration is out of reach in resource-limited regions due to the time and temperature restrictions, technical sophistication, and cost of reagents, in particular monoclonal antibodies to measure CD4 on blood cells, the only currently acceptable method. A commonly used cost-saving and time-saving laboratory strategy is to calculate, rather than measure certain blood values. For example, LDL levels are calculated using the measured levels of total cholesterol, HDL, and triglycerides. Thus, identification of cell-free correlates that directly regulate the number of CD4(+) T cells could provide an accurate method for calculating CD4 counts due to the physiological relevance of the correlates. The number of stem cells that enter blood and are destined to become circulating CD4(+) T cells is determined by the chemokine CXCL12 and its receptor CXCR4 due to their influence on locomotion. The process of stem cell locomotion into blood is additionally regulated by cell surface human leukocyte elastase (HLE(CS)) and the HLE(CS)-reactive active α(1)proteinase inhibitor (α(1)PI, α(1)antitrypsin, SerpinA1). In HIV-1 disease, α(1)PI is inactivated due to disease processes. In the early asymptomatic categories of HIV-1 disease, active α(1)PI was found to be below normal in 100% of untreated HIV-1 patients (median=12 μM, and to achieve normal levels during the symptomatic categories. This pattern has been attributed to immune inactivation, not to insufficient synthesis, proteolytic inactivation, or oxygenation. We observed that in HIV-1 subjects with >220 CD4 cells/μl, CD4 counts were correlated with serum levels of active α(1)PI (r(2)=0.93, p<0.0001, n=26) and inactive α(1)PI (r(2)=0.91, p<0.0001, n=26). Administration of α(1)PI to HIV-1 infected and uninfected subjects resulted in dramatic increases in CD4 counts suggesting α(1)PI participates in regulating the number of CD4(+) T cells in blood. With stimulation, whole saliva contains sufficient serous exudate (plasma containing proteinaceous material that passes through blood vessel walls into saliva) to allow measurement of active α(1)PI and the correlation of this measurement is evidence that it is an accurate method for calculating CD4 counts. Briefly, sialogogues such as chewing gum or citric acid stimulate the exudation of serum into whole mouth saliva. After stimulating serum exudation, the activity of serum α(1)PI in saliva is measured by its capacity to inhibit elastase activity. Porcine pancreatic elastase (PPE) is a readily available inexpensive source of elastase. PPE binds to α(1)PI forming a one-to-one complex that prevents PPE from cleaving its specific substrates, one of which is the colorimetric peptide, succinyl-L-Ala-L-Ala-L-Ala-p-nitroanilide (SA(3)NA). Incubating saliva with a saturating concentration of PPE for 10 min at room temperature allows the binding of PPE to all the active α(1)PI in saliva. The resulting inhibition of PPE by active α(1)PI can be measured by adding the PPE substrate SA(3)NA. (Figure 1). Although CD4 counts are measured in terms of blood volume (CD4 cells/μl), the concentration of α(1)PI in saliva is related to the concentration of serum in saliva, not to volume of saliva since volume can vary considerably during the day and person to person. However, virtually all the protein in saliva is due to serum content, and the protein content of saliva is measurable. Thus, active α(1)PI in saliva is calculated as a ratio to saliva protein content and is termed the α(1)PI Index. Results presented herein demonstrate that the α(1)PI Index provides an accurate and precise physiologic method for calculating CD4 counts.     

The clinical importance of CD4+CD7− in human diseases

The CD7 antigen is a member of the immunoglobulin superfamily that expresses on the surface of all thymocytes, a majority of mature T cells, and also natural killer cells. Interestingly, under physiological and different pathological conditions, the loss of CD7 antigen occurred in the subset of CD4⁺ memory T cells. Various functions have been proposed for CD7, including its role in the activation and intercellular adhesiveness of T cells. Several studies indicate that the number of CD4⁺CD7⁻ T cells increases in diseases such as chronic inflammation and T-cell malignancies, these being skin inflammatory lesions. Therefore, this can be useful for the diagnosis of cancer cells, especially with reference to blood origin, treatment monitoring, and establishment of new therapies. Therefore, a comprehensive review could be useful to increase our knowledge about the clinical importance of these cells in human disease.     

Nephro-protective effect of granulocyte colony-stimulating factor in streptozotocin induced diabetic rats

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor β1 (TGF-β1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-β1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.     

Lymphocyte subsets and viral load in patients with HIV-associated non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibody and chemotherapy

The anti-CD20 monoclonal antibody Rituximab is a novel antitumor agent used in association with chemotherapy (CT) for the treatment of high-grade/intermediate non-Hodgkin's lymphomas (NHL) in HIV-negative populations. This therapeutic combination is currently also being explored in HIV-positive patients with NHL (HIV-NHL). The objective of our study was to determine CD4 and CD8T cell counts, HIV plasma viremia and proviral load in patients with CD20-positive HIV-NHL treated with Rituximab plus CT and highly active antiretroviral therapy (HAART). We studied eight patients with HIV-NHL treated by anti-CD20 and CT before, after three, and after six cycles of therapy; CD4, CD8 and CD19 lymphocyte subsets were measured by monoclonal antibodies and flow cytometry. HIV plasma viremia was determined by the b-DNA assay, and proviral load by a quantitative competitive PCR. CD4T cell counts remained stable after three cycles of therapy, while a significant reduction of this subset was present at the end of therapy. HIV plasma viremia was significantly reduced after the third cycle, but returned to pretreatment levels at the end of therapy; we also observed individual fluctuations of proviral load during therapy, this marker being increased in two out of three patients at the end of therapy. These observations suggest that Rituximab plus CT accelerated the rate of CD4 depletion and of HIV replication in the peripheral blood of HIV-NHL patients and that HAART may be able to delay these effects. Received: 1 December 2000 / Accepted: 8 February 2001     

Factors affecting retrovirus-mediated gene transfer to human CD34+ cells

BACKGROUND: Retrovirus-mediated gene transfer is a useful technology in studying the biology of hematopoietic stem cells (HSCs) as well as in developing gene therapy products for a variety of human diseases. One of the most important factors determining the success of these studies is the number of HSCs receiving the gene of interest. METHODS: We tested various parameters for their influences on gene transfer efficiency to CD34+ cells derived from bone marrow. Based on a literature survey, three medium formulations of CD34+ cells have been compared for their effects on gene delivery efficiency and differentiation of them. We also tested whether FBS, used in the medium formulation, could be replaced with human serum or synthetic material. RESULTS: Formulation A, consisting of stem cell factor, Flt-3 ligand, thrombopoietin, and IL-3, provided optimum results in that it maintained the highest percentage of CD34+ cells during the culture as well as produced the highest gene delivery efficiency. It was found that the synthetic serum substitute containing bovine serum albumin, insulin and human transferrin could replace the fetal bovine serum present in the original formulation A without compromising gene transfer efficiency. When the transduction procedure was repeated three times, the gene could be delivered in up to 60% of the cell population. Gene delivery efficiency was comparable between CD34+ cells derived from bone marrow and mobilized peripheral blood. CONCLUSIONS: Our data could be useful in designing a procedure for stem cell gene therapy and providing a basis for further improving the conditions for gene transfer to various HSCs.     

Spatial and temporal distribution of Alternaria spores in the Iberian Peninsula atmosphere, and meteorological relationships: 1993–2009

This paper provides an updated of airborne Alternaria spore spatial and temporal distribution patterns in the Iberian Peninsula, using a common non-viable volumetric sampling method. The highest mean annual spore counts were recorded in Sevilla (39,418 spores), Mérida (33,744) and Málaga (12,947), while other sampling stations never exceeded 5,000. The same cities also recorded the highest mean daily spore counts (Sevilla 109 spores m^?3; Mérida 53 spores m^?3 and Málaga 35 spores m^?3) and the highest number of days on which counts exceeded the threshold levels required to trigger allergy symptoms (Sevilla 38 % and Mérida 30 % of days). Analysis of annual spore distribution patterns revealed either one or two peaks, depending on the location and prevailing climate of sampling stations. For all stations, average temperature was the weather parameter displaying the strongest positive correlation with airborne spore counts, whilst negative correlations were found for rainfall and relative humidity.     

The effect of different housing conditions on behavioural and adrenocortical reactions in veal calves

Veal calves were housed either tethered indoors on slatted floorings or loose in groups of eight in a semi-open barn with straw bedding. Six weeks after arrival at the station the calves were submitted to a 10-min open-field session in either the same environment as the one in which they were housed or in the alternative environment. During this session, activity, latency time to first movement and duration of immobility were scored and blood samples were taken for cortisol determination before and after the session. In both instances, the tethered calves exhibited higher activity scores and shorter periods of immobility. Plasma cortisol levels were significantly affected by testing conditions but not by housing conditions, i.e. plasma cortisol levels increased more when the animals were tested in a different environment from the one in which they were housed. Adrenal cortex response to repeated blood sampling and to ACTH injections was found to be significantly higher in tethered calves. These results show that housing conditions strongly influenced the behaviour and endocrine activity of the calves. The dynamics of these changes need further study.     

Characteristics of hematopoietic stem cells of umbilical cord blood

Umbilical cord blood collected from the postpartum placenta and cord is a rich source of hematopoietic stem cells (HSCs) and is an alternative to bone marrow transplantation. In this review we wanted to describe the differences (in phenotype, cytokine production, quantity and quality of cells) between stem cells from umbilical cord blood, bone marrow and peripheral blood. HSCs present in cord blood are more primitive than their counterparts in bone marrow or peripheral blood, and have several advantages including high proliferation. With using proper cytokine combination, HSCs can be effectively developed into different cell lines. This process is used in medicine, especially in hematology.     

Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation

Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n = 20) and recipients (n = 20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P < 0.001), maintain normal blood insulin levels (P < 0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P < 0.01), increased Foxp3 mRNA expression (P < 0.01) and increased Foxp3 protein expression (P < 0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.     

Cortisol responses to immobilization with Telazol or ketamine in baboons (Papio cynocephalus/anubis) and rhesus macaques (Macaca mulatta)

Little is known about the influence of Telazol on cortisol or of anesthetic agents on immunological measures, and reports of ketamine's effect on cortisol are inconsistent. We measured effects of Telazol, ketamine and blood sampling on cortisol in male rhesus macaques and male savannah baboons. We also obtained leukocyte counts in the macaques. In macaques, Telazol reduced cortisol in the morning but not in the afternoon; ketamine had no effect on cortisol in these animals. In baboons, cortisol changed little post-Telazol but increased post-ketamine. In macaques, lymphocyte numbers decreased following afternoon injection of Telazol, ketamine or saline. The injection and blood sampling process increased cortisol levels in monkeys not trained to extend an arm but exerted no effect on cortisol in trained macaques. Thus, the animals' physiological responses to blood sampling and immobilization are influenced by such variables as anesthetic agent, species, time of day, and familiarity with the blood sampling process.