IL-4与IL-10联合诱导异种骨移植免疫耐受的体外研究

目的　探讨 IL - 4和 IL - 10在诱导异种骨移植免疫耐受中的作用。方法　反应细胞为 BAL B/c小鼠脾淋巴细胞 ,刺激细胞为新西兰白兔血淋巴细胞 ,刺激抗原为兔骨上清液。采用经典的混合淋巴细胞培养法及骨上清液与淋巴细胞混合培养法作为异种骨移植的体外实验模型。在各培养液中分别加入 IL - 4、IL - 10及两者联合应用 ,通过测定其 3H- Td R掺入率 ,观察不同细胞因子对刺激淋巴细胞增殖的影响。结果　无论在细胞刺激组还是骨上清液刺激组 ,IL- 4对淋巴细胞增殖均有显著抑制作用 (P<0 .0 0 1和 P<0 .0 5 ) ,IL- 10未表现出抑制作用 (P>0 .0 5 )。在两组 IL- 4和 IL - 10联合应用均产生比 IL - 4单独应用更为明显的细胞增殖抑制作用 (P<0 .0 0 1和 P<0 .0 5 )。结论　 IL - 4对由细胞或骨上清液刺激产生的淋巴细胞增殖均有很好的抑制作用 ,IL- 10没有表现出抑制作用 ;IL- 4与 IL- 10联合应用有协同抑制作用。     

胃饲乙醇预处理诱导肝脏缺血耐受性的可行性探讨

目的探讨胃饲乙醇预处理对肝脏缺血再灌流损伤的影响,并初步评价其预处理的可行性。方法40%乙醇胃饲Wistar大鼠。分组:①大鼠36只,随机分6组:A组8g/kg、B组7g/kg、C组6g/kg、D组5g/kg、E组4g/kg、正常组0g/kg;以中毒症状及肝组织病理为指标,判定大鼠乙醇急性中毒剂量。②大鼠78只,随机分为4组:正常对照组(N)、单纯乙醇组(E)、单纯缺血组(ISCH)、胃饲乙醇预处理组(EPC);采用尾叶转流下的肝缺血模型,于再灌流3、6、12、24h留取标本。结果急性胃饲乙醇≤5g/kg预处理后,动物中毒症状轻,无死亡;乙醇预处理可以在一定程度上减轻肝脏90min的缺血再灌流损伤。结论适当剂量的乙醇胃饲预处理是一种安全的预处理措施,有望成为增强肝脏对缺血再灌流损伤耐受性的一种较好的预处理方式。     

IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.     

The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy

Abstract Over the past 15–20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.     

Central circulation in rats with different tolerance to acute blood loss

Study of the dynamics of cardiac output in rats with different tolerance to acute massive blood loss showed that the pumping ability of the heart remains intact during the entire posthemorrhagic period in all high-resistant and in 65% low-resistant rats. In 35% rats that were low-resistant to blood loss, the cardiac output deficiency syndrome developed after cessation of bleeding against the background fall in arterial pressure and a decrease in the hepatic blood flow, which are the signs of rapid variant of the dysfunction produced by acute blood loss. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 384–388, October, 1998     

Antigen Presentation By Class I Major Histocompatibility Complex Molecules: A Context for Thinking About HLA-G

PROBLEM: There is substantial data that support the efficacy of paternal leukocyte immunization (PLI) for the treatment of alloimmune mediated miscarriage; however, there is confusion regarding the laboratory test that should be performed to determine levels of maternal anti-paternal leukocyte antibodies (MAPLA). METHOD: Popular methodologies employed include: 1) microcytotoxicity (MCX), 2) mixed lymphocyte culture (MLC), and 3) cell flow cytometry crossmatch (FCXM). Cell flow cytometry crossmatch correlates well with the more difficult MLC assay although the former proves the more sensitive study. This work compares the MCX assays with FCXM. The study group consisted of ten women who had a history of three or more spontaneous abortions (SABs). All ten had very low levels (<10%) of MAPLA as measured by FCXM. Following PLI all subjects demonstrated elevated levels (>50%) of MAPLA by FCXM. At 12 weeks gestation, sera were simultaneously measured for MAPLA by MCX and FCXM. RESULTS: Although all ten patients had very high levels of MAPLA by FCXM during pregnancy, five of ten had antibodies to HLA Class I and two of ten had antibodies to HLA Class II paternal antigens by MCX. Furthermore, all patients who were positive by MCX to paternal Class I antigens were also positive to Class I antigens not seen in either parent. Both patients who were positive by MCX to paternal Class II antigens were also positive to maternal Class II antigens. Notable is that all ten women eventually delivered healthy infants. CONCLUSION: Based on this preliminary study, the MCX assay is neither sensitive or reliable enough to determine the need and/or to monitor the effectiveness of PLI. Flow cytometry should be the modality of choice when determining the need for alloimmunotherapy and to monitor the effectiveness of treatment.     

恒河猴坐姿着陆冲击内耳损伤的观察

为研究机体及各组织器官对冲击力的耐受限值，探讨致伤原因及提出防护措施，利用着陆冲击塔，使实验动物恒河猴的坐姿状态下，进行冲击试验，试验后１ｈ左右处死，作大体解剖观察并取心，肝，脾，肺，颞骨等组织，固定，切片，镜检。同时重点观察了内耳的损伤。结果表明，冲击载荷不大（平台过载值为≤２５Ｇ）时内脏虽然有轻度损伤，但内耳可避免受员，当冲击力加大到一定程度（平台过载值为３０～３５Ｇ）导致内脏中等损伤时，内耳     

The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

Ocular Pharmacokinetics and Pharmacodynamics of Phenylephrine and Phenylephrine Oxazolidine in Rabbit Eyes

The aqueous humor concentration of phenylephrine and its corresponding mydriatic response were measured over time in New Zealand albino rabbit eyes following a 10-µl topical instillation of a phenylephrine HC1 viscous solution (10%) or a phenylephrine oxazolidine (prodrug) suspension in sesame oil (1 and 10%). The bioavailability of a 1% prodrug suspension in the rabbit eye (AUC of aqueous humor concentration vs time) was 30% lower than that of a 10% phenylephrine solution (P < 0.1) with the exception that the peak time occurred 34 min earlier with the prodrug. A 10% prodrug suspension increased the aqueous humor bioavailability approximately eightfold but improved the mydriatic activity (AUC of mydriasis vs time) only fourfold. The pharmacokinetic parameters, apparent absorption, and elimination rate constants, of phenylephrine and the prodrug were determined from aqueous humor concentration–time and mydriasis–time profiles. The study showed that the kinetic parameters of phenylephrine estimated from its mydriasis profile do not accurately reflect the kinetics of drug distribution in the iris. These parameters also varied with the instillation of phenylephrine solution or prodrug suspensions. A mydriatic tolerance of the pupil response was apparent after the topical instillation of phenylephrine solution. The mydriatic tolerance may be due to the decrease in receptor number in the iris dilator muscle.     

Oral tolerance in EAE: reversal of tolerance by T helper cell cytokines

Oral administration of myelin basic protein (MBP) inhibits clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE), but only partially reduces serum anti-MBP antibody titers. We report here that orally administered MBP alters the isotypic distribution of anti-MBP antibody-forming cells (AFC) among various lymphoid tissues, with the most profound differences seen in mucosal tissues. We observed an isotype-selective reduction in anti-MBP IgA but not IgM AFC frequencies in Peyer's patches. The anti-MBP IgA AFC frequencies could be reconstituted by addition of interleukin 4 (IL-4) and interleukin 5 (IL-5). The cytokines did not appear to generate de novo responses since no increases in anti-MBP IgA AFC frequencies were observed in control cultures. These results indicate that decreased antibody production, as a result of oral antigen administration, can be reversed by exposure to the appropriate cytokines.