Mixed leukocyte reactions and histocompatibility in rats

Mixed leukocyte culture tests have been carried out on two hetero geneous but genetically defined backcross populations of rats to determine whether the reactions observed can provide the basis for histocompatibility matching. The experiments were designed so that only-one-way reactions could occur. Only when the donors of individual leukocyte mixtures differed at the important Ag-B histocompatibility locus was there any in vitro reactivity, and differences at this locus were invariably associated with the prompt rejection of skin homografts. Determination of compatibility at this locus proved to be important in that it facilitated the prolongation of survival of skin homografts by immunosuppressive therapy.     

重组人白介素-10对兔皮肤移植排斥反应及外周血T细胞亚群的影响

目的 观察重组人白介素-10（rhIL-10）对白兔皮肤移植排斥反应及外周血T细胞亚群的影响.方法 36只白兔随机等分为供体组和受体组,再将18只受体白兔随机分为rhIL-10组（5、10μg·kg-1·d-1）、环孢素（CsA）阳性对照组（5、10 mg· kg-1·d-1）、rhIL-10＋ CsA联合组（5μg·kg-1·d-1 hIL-10＋5 mg·kg-1·d-1 CsA）、生理盐水阴性对照组（1 mL/d）.在移植前1d至术后8d连续肌注药物,观察各组皮片移植排斥反应情况及外周血CD4＋和CD8＋细胞数、CD4/CD8细胞比值.结果 rhIL-10组排斥反应发生时间比阴性对照组延长（P＜0.05）,而rhIL-10＋ CsA组排斥反应发生时间比低剂量rhIL-10及CsA组延长（P＜0.05）.在发生急性排斥反应时,CD4＋细胞数及CD4/CD8细胞比值升高,在皮片坏死时达到峰值.结论 rhIL-10可抑制白兔皮肤移植排斥反应,CD4/CD8细胞比值有助于监测排斥反应发生.     

Mosaic histocompatibility of skin grafts from female mice

The histoincompatibility determined by one or more genes on the X chromosome of the mouse effects a complete rejection of skin of the (C57BL/6 female symbol x BALB/c male symbol) F(1) hybrid male grafted onto the reciprocal type F(1) hybrid male, but only an incomplete rejection of either reciprocal type F(1) hybrid female skin, grafted onto the same type of male host. The resulting mosaic survival pattern of the female graft is interpreted as support for the Lyon hypothesis of X-chromosome inactivation.     

Identification of the miniature pig inbred line by skin allograft

Skin grafting has been used as one of the most reliable tests to determine the genetic stability of laboratory animal such as mice and rats inbred line, but no identification of swine inbred lines by skin grafting has been reported. At present, Wuzhishan miniature pig(WZSP) inbred line has acquired the F24 individuals in China. In order to verify whether WZSP inbred line had been cultivated successfully, allogeneic skin grafts and related research were performed on F20 individuals of WZSP inbreeding population, compared with a control group of autologous transplantation. We observed the transplant recipients' wounds, detected peripheral blood-related indicators interleukin-2, 4 and 10, CD4+ and CD8+ lymphocytes, and conducted hematoxylin-eosin(HE) and Masson's staining of skin to judge whether the immune rejection reactions occurred within 28 days after transplantation. Chr. 7 genomic heterozygosity of 48 WZSP individuals from F20 to F22 was analyzed by high-density single nucleotide polymorphism(SNP) chips(60 000 SNPs). The result showed that there were no significant differences in graft skin, the plasma interleukin-2, 4, 10, CD4+ and CD8+, HE and Masson's staining results between the allograft and autograft groups, and no immune rejection occurred on the allograft group. We found that 11 genes in Chr. 7 of major histocompatibility complex(MHC) I and MHC II were homozygous which confirmed that immune antibody of the allograft and autograft groups were highly identical and also provided a theoretical basis to no immune rejection occurred on the allograft in the inbred WZSP. The result proved that the WZSP inbred line had been cultivated successfully for the first time in the world. The test methods also provide a scientific basis for the identification of swine and mammal inbred lines.     

Genetic background and expressivity of histocompatibility genes

A difference in the reactivity of F(1) hybrid female mice to skin grafts from male donors of each of their parental strains suggests that the genetic background can influence the efficacy of the Y antigen to elicit rejection of the graft.     

Allografts in genetically defined rats: difference in survival between kidney and skin

Although skin allografts from inbred donors of the Fisher strain to inbred male Lewis recipients regularly show acute rejection within 12 days, orthotopic kidney allografts between untreated animals, in this same combination of strains, usually remain functionally intact for longer than 100 days. Since such renal allografts persist despite previous or concomitant rejection of skin allografts, neither acquired tolerance nor nonspecific immunosuppression can explain the surprisingly prolonged kidney survival. Many factors appear to be responsible for the disparate survival times observed. Tentatively, these factors are (i) antigenic differences between kidney and skin, (ii) intervention of immunological enhancement, and (iii) physiological differences in vulnerability between kidney and skin.     

HOMOGRAFT REJECTION IN THE FETAL LAMB: THE ROLE OF CIRCULATING ANTIBODY

Specific rejection of sterile orthotopic skin homografts by the fetal lamb in utero was unaccompanied by the presence of plasma cells in either the graft and its bed, or in the reactive draining lymph node. The grafts appeared not to stimulate the production of circulating immunoglobulins. The presence in the fetal circulation of rabbit anti-sheep 7S gamma-globulin and anti-beta(2M)-globulin did not inhibit the normal course of homograft rejection. These data support the contention that conventional circulating antibody is not an obligatory participant in the rejection of solid-tissue homografts.     

Effects of Rapamycin on the Differentiation and Function of Macrophages In Vitro

Macrophages have been generated from bone marrow progenitor cells （BMPCs） with macrophage colony-stimulating factor （M-CSF）. Rapamycin （rapa） is an immunosuppressive drug, which could prevent renal graft rejection and inhibit tumor growth to yield antiproliferative activity in a variety of malignancies. However, the direct effect of rapa on the development of macrophages is unknown. In this study, we explored the direct effect of rapa on the differentiation and function of macrophages differentiated from mouse BMPCs in vitro in the presence of M-CSF. The experimental data showed that rapa prevented the differentiation of macrophagcs by down-regulating CD80 and CD86 expression but upregulating F4/80 expression, as well as by reducing the capacity of differentiated macrophages to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction. Furthermore, the phagocytic capacity of differentiated macrophages was significantly reduced by rapa. Therefore, rapa may directly inhibit macrophage differentiation and function, which may have been one of the major targets for rapa to mediate its immunosuppressive properties.     

Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants

T cells that accompany allogeneic hematopoietic grafts for treating leukemia enhance engraftment and mediate the graft-versus-leukemia effect. Unfortunately, alloreactive T cells also cause graft-versus-host disease (GVHD). T cell depletion prevents GVHD but increases the risk of graft rejection and leukemic relapse. In human transplants, we show that donor-versus-recipient natural killer (NK)-cell alloreactivity could eliminate leukemia relapse and graft rejection and protect patients against GVHD. In mice, the pretransplant infusion of alloreactive NK cells obviated the need for high-intensity conditioning and reduced GVHD. NK cell alloreactivity may thus provide a powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.     

Serologically defined (SD) locus in cattle

Using cytotoxic serums obtained from multiparous cows or by alloimmunization, we have detected 11 lymphocyte antigens controlled by codominant alleles at a serologically defined locus called BoLA-A (bovine lymphocyte antigens). This locus, along with the lymphocyte defined loci previously reported, establishes the existence of a major histocompatibility system of cattle.     

Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets

Malaria remains a devastating disease largely because of widespread drug resistance. New drugs and a better understanding of the mechanisms of drug action and resistance are essential for fulfilling the promise of eradicating malaria. Using high-throughput chemical screening and genome-wide association analysis, we identified 32 highly active compounds and genetic loci associated with differential chemical phenotypes (DCPs), defined as greater than or equal to fivefold differences in half-maximum inhibitor concentration (IC(50)) between parasite lines. Chromosomal loci associated with 49 DCPs were confirmed by linkage analysis and tests of genetically modified parasites, including three genes that were linked to 96% of the DCPs. Drugs whose responses mapped to wild-type or mutant pfcrt alleles were tested in combination in vitro and in vivo, which yielded promising new leads for antimalarial treatments.     

Homograft rejection delayed by treatment of donor tissue in vitro with antilymphocyte serum

Treatment of rabbit corneal tissue in vitro with pooled rabbit serum delays the onset of corneal homograft rejection in the host. Addition of antilymphocyte serum results in a further significant delay in the onlset of rejection. The mechanisms by which such treatment of donor tissues may modify the antigenic content of the material are discussed.     

纤维蛋白胶应用于犬自体网状皮片移植效果的观察

为探究纤维蛋白胶(fibrin glue,FG)应用于犬自体网状皮片移植术中的效果,选取15只犬作为试验动物,于两前肢建立3 cm×4 cm的全层皮肤缺损模型,以胸背部作为供皮区,将纤维蛋白胶应用于网状皮片移植术中,以单纯网状皮片移植为对照,于术后第3、5、7、14、28天随机选取3只进行大体观察和移植皮片局部观察,并制备石蜡切片进行组织学观察。皮片局部观察结果显示,试验组红肿、渗出较对照组轻微,炎性反应期短;术后28 d,所有皮片生长良好,试验组线性瘢痕较对照组轻。组织学观察结果显示,试验组较对照组炎性细胞的浸润期短,胶原纤维排列规则,皮肤附属结构完整。结果表明,纤维蛋白胶可缩短创面炎性反应期,增强局部组织修复能力,减少瘢痕的过度增生,可使成活后的移植皮片结构和功能更接近正常皮肤。     

The influence of allogeneic cells on the human T and B cell repertoire

Clinical transplantation is often complicated by rejection episodes, in which the immune system of the recipient reacts to the foreign transplantation (HLA) antigens on the graft. This immune response includes humoral and cellular components. In the first, B lymphocytes form antibodies to the HLA alloantigens. In the second, CD8+ T lymphocytes recognize and react to HLA class I antigens, and CD4+ T cells react to HLA class II antigens. The frequency and severity of these rejection episodes can be diminished by immunosuppressive drugs, HLA matching between donor and recipient, and immune modulation by blood transfusion. Effective HLA matching between donor and recipient is not always possible and often not necessary. Insight into the factors that influence the T and B cell repertoire after blood transfusion might lead to new approaches to improve graft survival.     

Effect of stress on skin transplantation immunity in mice

Chronic avoidance-learning stress was found to depress the immune reaction responsible for skin homograft rejection to a modest but significant degree. This effect was observed in a genetically uniform as well as a heterogeneous line of mice.     

Leukemia virus activation during homograft rejection

Activation of murine leukemia viruses, as detected by the mixed culture cytopathogenicity (XC) assay, followed the transplantation of A/J skin onto immunosuppressed BALB/c mice. Virus was found in most of the mice receiving both skin grafts and antilymphocyte serum, but not in animals receiving either the serum alone, skin graft alone, or no treatment.     

Specific tissue graft rejection in earthworms

Earthworms are capable of destroying antigenic tissues. Autogeneis transplants healed in regularly and remained permanently viable. Xenografts, by contrast were cicatrized but eventually rejected. Intrafamilial transplants survived longer than interfamilial ones. Xenografts and autografts placed in the graft bed were joined to each other but xenografts were later destroyed although autografts were not. Two xenografts from Eisenia to Lumbricus, performed simul taneously, showed survival endpoints similar to a single xenograft. A 5-day interval between first- and second-set grafting led to an accelerated rejection of both transplants. First-set Allolobophora transplants to Lumbricus performed simulataneously with second-set Eisenia grafts were destroyed at a time different from either of the two Eisenia transplants. A single Allolobophora transplant to Lumbricus was rejected at survival tines equivalent to Allolobophora along with two Eisenia transplants.     

白桦不同嫁接方法与成活率的关系

以５－６年生白桦野生苗作砧木，在１５－１７年生白桦优树上采集接穗，采用水培靠接，髓心形成层贴接，无顶芽劈接等１０种方法进行嫁接，通过方差分析，盯关分析，偏相关分析等方法对各种嫁接法的成活率，生长量及物候性状进行系统地统计分析研究。研究结果表明：白桦不同嫁接方法其成活率有显著差异，水培靠接与髓心形成层贴接成活率较高，分别８５．２％，４７．４％；不同嫁接方法生长性状上差异显著，水培靠接法当年生长量和叶     

Mismatch repair, but not heteroduplex rejection, is temporally coupled to DNA replication

In eukaryotes, it is unknown whether mismatch repair (MMR) is temporally coupled to DNA replication and how strand-specific MMR is directed. We fused Saccharomyces cerevisiae MSH6 with cyclins to restrict the availability of the Msh2-Msh6 mismatch recognition complex to either S phase or G2/M phase of the cell cycle. The Msh6-S cyclin fusion was proficient for suppressing mutations at three loci that replicate at mid-S phase, whereas the Msh6-G2/M cyclin fusion was defective. However, the Msh6-G2/M cyclin fusion was functional for MMR at a very late-replicating region of the genome. In contrast, the heteroduplex rejection function of MMR during recombination was partially functional during both S phase and G2/M phase. These results indicate a temporal coupling of MMR, but not heteroduplex rejection, to DNA replication.     

Relationship of blood type to histocompatibility in chickens

Evidence shows that the B blood group locus in chickens, which controls red cell antigens, is associated with tolerance of skin homografts. Three other blood group loci studied did not show this effect.