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异基因嵌合体与移植耐受关系的研究Ⅱ.成年小鼠联体共生诱导耐?… 总被引:1,自引:0,他引:1
将BALB/c(H-2^d)小鼠及C57BL/H(H-2^d,B6)小鼠的脾细胞分别经尾静脉注射给对方,2d后再分别腹腔注射环磷胺(CY)150mg/kg,CY注射后1d对BALB/c及B6小鼠进行联体(parabiosis),1周后分开并进行相互间的植皮。发现BALB/c小鼠对B6小鼠的皮肤耐受期明显延长(MST=25.7d),但是B6对BALB/c及B6小鼠在联体分开后的第1天和第30天进行胸 相似文献
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目的:探讨供体源的异基因血细胞嵌合体与受体耐受状态的关系,在不同品系的成年小鼠成功地建立了联体模型。方法:Alb/c(H-2^d)小鼠经尾静脉注入C57BL/6(H-2^d,B6)脾细胞,同时C57BL/6(B6)小鼠经尾静脉注入Balb/c小鼠脾细胞,2d后,分别给Balb/c及B6小鼠腹腔注射环磷酰胺(CY),可以明显延长Balb/c与B6联体小鼠的存活期(MST=30.4d)。对经以上处理的 相似文献
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本文用门静脉注射异型脾细胞加腹腔注射环磷酰胺方法,成功地诱导了成年Balb/c小鼠(H-2d)对C57BL/6(H-2b)小鼠的免疫耐受。致死照射的耐受Balb/c小鼠用C57BL/6(B6)小鼠的胎肝细胞移植后,无移植排斥产生。嵌合状态分析的结果表明,在胎肝移植后90d和240d,重建的Balb/c小鼠的脾细胞分别有74.4%和83.7%来自于供体B6小鼠.证明B6小鼠胎肝造血干细胞已经在致死照射的Balb/c小鼠体内稳定植入。免疫功能检测的结果表明,在胎肝移植后90d,照射Balb/c小鼠的免疫功能已经重建。 相似文献
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目的:探讨高压氧降低细胞免疫功能、抗移植排斥反应的机理。方法:供鼠BALBC(H-2d),受鼠C57BL6(H-2b),皮肤移植后,分对照组、实验组,实验组小鼠用99-2%氧气,0-25MPa,作用1-5h,每日一次,看高压氧对小鼠移植皮片存活时间的影响,分别于术后3d、7d、14d、21d检测小鼠脾Thy-2阳性细胞、L3T4阳性细胞、Lyt-2阳性细胞百分率的变化及IL-2产生量、对IL-2R反应性,同时做ThTs比值变化的比较。另外,于术后14d,应用免疫组化法检测移植皮片局部CD+… 相似文献
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通过胸腺内注射质粒PXN(N2-B19-H-2K^b),表达外源性主要组织相容性抗原复合物(majorhisto-compatibilitycomplex,MHC)抗原,为下一步诱导异基因小鼠器官移植耐受作准备。方法:通过BALB/C小鼠有腺内注射射质粒PXN(N2-B19-H-2K^b),将外源性的编码C57BL/6小鼠MHCⅠ类抗原的H-2K^bcDNA转移到BALB/C小鼠胸腺,用聚合酶链反 相似文献
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成年小鼠皮肤移植耐受诱导的实验研究 总被引:11,自引:1,他引:11
静脉注射BaIb/c小鼠(H-2 ̄d)脾细胞和骨髓细胞,48小时后,腹腔注射环磷酰胺和抗胸腺细胞血清,可诱导B6小鼠(H-2 ̄b)对BaIb/c小鼠皮肤移植的长期耐受(>80天).耐受B6小鼠可正常排斥无关品系CBA/J小鼠(H-2 ̄k)的皮肤,显示了耐受的特异性。上述诱导方案可导致受体小鼠脾细胞对ConA、LPS诱导的增植反应的抑制,但这种全身性免疫抑制可在短期内恢复,而供体特异性的同种异型反应,如MLR和DTH则不能恢复。 相似文献
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H—2^b和H—2^d单体型小鼠MHC I类分子结合的HFRSV蛋白抗 … 总被引:1,自引:0,他引:1
本文通过对H-2^b和和H-2^d单体型小鼠主要组织相容性抗原I类分子结合抗原肽的分析,建立了一个计算机预测模型,并对肾综合征出血热病毒核蛋白(NP)及囊膜糖蛋白G1和G2可与Balb/c小鼠(H-2^d)和C57BL/6(H-2^b)小鼠MHC I类分子相结合的抗原表位进行了分析,预测出可分别与H-2K^b,H-2D^d,H-2D^d和H-2L^d结合的核蛋白表位,依此各有7,14,4,0和8个 相似文献
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目的 离体实验中,异型反应性CD4^+T淋巴细胞可以通过识别由受体抗原提呈细胞(APC)提呈的异体MHC-I类抗原这一“间接途径”崦活化增殖。在体内是否能导致MHC-I类分子差异的异体移植排斥反应值得研究。方法 CD8基因被剔除的小鼠(knockout mice)体内99%以上的T淋巴细胞为CD4^+T细胞。将MHC-I类分子发生基因变异的C57BL/6小鼠(B6K^bml,H-2^bml,K^b 相似文献
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高压氧抗小鼠同种皮肤移植排斥反应的实验研究 总被引:1,自引:0,他引:1
目的:探讨高压氧抗移植排斥反应机理。方法:C57BL/6小鼠接受BALB/c小鼠移植皮片后,在992%O2,025mPa条件下每天1h直至皮片排斥。动态观察移植局部T细胞及亚群,IL-2R(α)阳性细胞浸润情况以及混合淋巴细胞培养(MLC)、细胞杀伤活性(LMC)等。结果:高压氧组小鼠移植皮片存活时间明显延长;移植局部Thy-1,L3T4,Lyt-2及IL-2R(α)阳性细胞浸润明显减少,MLC及LMC均降低。结论:高压氧可通过抑制移植局部T淋巴细胞浸润及IL-2R表达以及H-2诱导的增殖反应及杀伤活性,从而抑制移植排斥反应。 相似文献
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K Huygen D Abramowicz P Vandenbussche F Jacobs J De Bruyn A Kentos A Drowart J P Van Vooren M Goldman 《Infection and immunity》1992,60(7):2880-2886
Three susceptible mouse strains, i.e., BALB/c (H-2d), C57BL/6 (H-2b), and major histocompatibility complex-congenic BALB.B10 (H-2b), were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and analyzed 4 weeks later for in vitro spleen cell cytokine secretion in response to purified protein derivative (PPD), BCG culture filtrate (CF), BCG cellular extract, total BCG, the purified extracellular 30-32-kDa antigen (the fibronectin-binding antigen 85), or the intracellular 65-kDa heat shock protein. C57BL/6 and BALB.B10 mice produced 5- to 10-fold more gamma interferon and interleukin-2 (IL-2) when stimulated with CF, PPD, and antigen 85 than BALB/c mice did. When stimulated with BCG extract and whole BCG, gamma interferon and IL-2 levels were generally lower and comparable in the three strains. IL-4 was detected in spleen cell culture supernatants from infected BALB/c mice but not from C57BL/6 or BALB.B10 mice. IL-5 could not be detected. C57BL/6 and BALB.B10 spleen cells also produced more tumor necrosis factor alpha and IL-6 after stimulation with PPD and CF than BALB/c cells did. Finally, BCG vaccination generated efficient protective immunity in C57BL/6 and BALB.B10 mice but not in BALB/c mice. These data suggest that secreted mycobacterial CF antigens selectively induce a strong TH1 response in BCG-infected C57BL/6 and BALB.B10 mice, whereas in BALB/c mice this response is partly counterbalanced by TH2 cells. 相似文献
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B Shankar S Premachandran S D Bharambe P Sundaresan K B Sainis 《Immunology letters》1999,68(2-3):237-245
Acute as well as fractionated whole body exposures to low doses (< 50 cGy) of ionizing radiation (LDR) have been reported to alter several immunological parameters in experimental animals. It is, however, not clear whether the augmentation of immune response by LDR will be observed for all responses and across genetic barriers. Since several proteins including p53 are synthesized following radiation exposure, the role of p53 and consequently that of activation induced apoptosis in the immunomodulation by LDR also remained to be evaluated. Experiments were, therefore, carried out in two different strains of inbred mice viz. C57BL/6 and BALB/c, exposed to fractionated LDR (4 cGy/day, 5 days/week, total dose 20 cGy) and subsequently stimulated with the polyclonal mitogen Con A or immunized with Mycobacterium vaccae or dinitrofluorobenzene (DNFB) for delayed type hypersensitivity (DTH) response. The proliferation of spleen cells in response to con A as measured by [3H]thymidine incorporation was significantly higher in 20 cGy-irradiated C57BL/6 mice as compared with that in the Con A-stimulated cells from sham-irradiated controls. The same response was suppressed by LDR in BALB/c mice. On the other hand, DTH to M. vaccae as well as DNFB was suppressed in C57BL/6 mice while DTH to M. vaccae was augmented in BALB/c mice and that to DNFB was not significantly affected following same dose. The augmentation of response to con A in C57BL/6 mice was prominent in CD4- (CD8+) T cells and was marked by the decrease in the proportion of cells expressing p53 as estimated by flow cytometry. Reduction in expression of p53 was accompanied by reduced apoptosis, as measured by TUNEL assay, in the Con A-stimulated spleen cells of irradiated C57BL/6 mice when compared with that in the sham-treated controls. The spleen cells of BALB/c mice showed exactly opposite profiles in this respect. Thus alteration in the immune response following LDR depends on antigen, type of response as well as the strain of mice used. Furthermore, the alterations in the expression of pro-apoptosis gene p53 and activation induced apoptosis in the effector or regulatory cells seem to contribute to the end result. 相似文献
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The injection of spleen cells from F1 mice into-newborns from a parental strain results in the establishment of cytolytic tolerance to donor alloantigens and the development of a lupus-like disease. This syndrome is the consequence of the recognition by alloreactive host CD4+ T cells of discordant major histocompatibility complex (MHC) class II antigens on semi-allogeneic donor B cells. We have analysed whether completely allogeneic spleen cells are as able as semi-allogeneic spleen cells to induce cytolytic tolerance to donor alloantigens and to co-operate with alloreactive T cells for autoantibody production. BALB/c mice were injected at birth with Thy-1-depleted spleen cells from (C57BL/6 x BALB/c)F1 or C57BL/6 mice, either alone or in combination. Cytolytic tolerance was always induced, as manifested by persistence of chimerism and acceptance of skin allografts. However, only F1 semi-allogeneic B cells were activated by alloreactive host T cells to produce anti-DNA IgG antibody. The deficient co-operation between BALB/c CD4+ T cells and completely allogeneic C57BL/6 B cells was confirmed after neonatal injection of (C57BL/ 6 x BALB/c)F1(Igha) spleen cells together with C57BL/6(Ighb) spleen cells. These mice developed anti-DNA antibodies bearing only the Igha allotype. Similar results were observed in experiments of allogeneic interaction in vitro, in which BALB/c CD4+ T cells were cocultured with either (C57BL/6 x BALB/c)F1 or C57BL/6 B cells. The present results demonstrate that completely allogeneic spleen cells efficiently induced cytolytic unresponsiveness to donor alloantigens, but B cells contained in this spleen cell population were unable to establish allo-helper interactions with alloreactive CD4+ T cells, suggesting that cytolytic and helper T-cell interactions involved in alloreactivity may be different. 相似文献
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Planelles L Thomas MC Marañón C Morell M López MC 《Clinical and experimental immunology》2003,131(1):41-47
Differential aspects of the host immune response generated by Trypanosoma cruzi infection were examined in two different mouse strains, BALB/c (haplotype H2-Kd) which does not overcome the acute phase of the infection and C57BL/6 (haplotype H2-Kb) which survives to the acute phase. After infection an increase in CD3+ T cells was observed in both mouse strains in the peritoneal cavity. However, while the CD3+ T cells from the BALB/c mice showed an increase in the IL-4 cytokine expression level, the same type of cells from the C57BL/6 mice showed an increase in IFN-gamma expression. In addition, only the macrophages from the C57BL/6 mice were activated secreting IL-12 and TNF-alpha and producing, moreover, high levels of nitrites. It was observed that also after parasite infection the expression of macrophage and dendritic cells CD40 and CD86 co-stimulation molecules from the spleen were diminished in BALB/c but not in C57BL/6 mice. In correlation with this observation the macrophages from the spleen of infected BALB/c mice secreted lower concentrations of nitrites than the C57BL/6 mouse cells. Also, the spleen dendritic cells from infected BALB/c mice had a small potential to present alloantigens in contrast to that observed in the infected C57BL/6 mouse cells. 相似文献
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静息B细胞体外诱导同种T细胞低反应的实验研究 总被引:3,自引:2,他引:1
本文采用体外同种混合淋巴细胞实验系统观察了静息B细胞 (restingBcell)诱导的同种免疫低应答反应。C5 7BL/6小鼠脾细胞经贴壁去除巨噬细胞后 ,用抗Thy 1抗体加补体和Percoll非连续密度梯度离心法分离 ,获得纯化的静息B细胞 ,经FACS检测其表面高表达SmIg (94 88% )和处于细胞分裂的G0 期 (95 79% ) ,并表达H 2Kb(99 5 % )和H 2I Ab(82 42 % ) ,但低表达CD80 /CD86 (分别为 4 2 6 %和 4 16 % )。C5 7BL/6小鼠静息B细胞刺激同种BALB/c小鼠T细胞 (初次MLR)只呈现微弱增殖反应 ,明显低于用LPS活化B细胞或全脾细胞刺激时的反应值。作再次MLR实验时 ,经初次MLR处理的T细胞对C5 7BL/6小鼠脾细胞表现为很弱的应答反应 ,但对无关的第三品系AKR鼠脾细胞却呈现强应答 ,说明这种应答低下具有相对特异性。上述结果提示 ,静息B细胞在MLR系统中不能诱导同种T细胞的充分活化而表现为同种免疫应答的低下。这在同种移植中诱导受体对移植物耐受提供有益的启示。 相似文献
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H60a is a minor histocompatibility antigen expressed in BALB and 129/Sv but not C57BL/6 mouse strains. The majority of CD8+ T cells in C57BL/6 mice responding to BALB.B splenocytes are specific for H60a. Interestingly, H60a is expressed constitutively on tumour cells, but its nature as a tumour rejection antigen, as a parallel to its function as a transplant rejection antigen, has not been studied. In this report, we show that tumour cells that constitutively express H60a at the cell surface can be recognized by H60a-specific T cells. Furthermore, when H60a-expressing sarcoma cell lines are transplanted into C57BL/6 mice, H60a-specific T cells can be found at high percentages among the tumour-infiltrating CD8+ T cells. These findings were seen in C57BL/6 but not F1 (C57BL/6×129) mice (which express H60a), suggesting that endogenous tolerance mechanisms suppress the antigenic properties of H60a. Our findings have implications for the generation of tumour vaccines against human natural killer group 2D ligands, such as MHC class I chain-like gene A, that are also transplantation antigens. 相似文献
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DNA vaccination with genes encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2 induces partially protective immunity against lethal challenge in mice 总被引:26,自引:0,他引:26
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Vercammen M Scorza T Huygen K De Braekeleer J Diet R Jacobs D Saman E Verschueren H 《Infection and immunity》2000,68(1):38-45
C57BL/6, C3H, and BALB/c mice were vaccinated with plasmids encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2, previously described as strong inducers of immunity. Seroconversion for the relevant antigen was obtained in the majority of the animals. T. gondii lysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-gamma) in spleen cell cultures from vaccinated BALB/c and C3H mice but not in those from control mice. Although not proliferating, stimulated splenocytes from DNA-vaccinated C57BL/6 mice also produced IFN-gamma. No interleukin-4 was detected in the supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio of specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-vaccinated C3H mice, suggesting that a Th1-type response had been induced. For BALB/c mice, the isotype ratio of the antibody response to DNA vaccination was less polarized. The protective potential of DNA vaccination was demonstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cysts of two different T. gondii strains: survival rates increased from 10% in controls to at least 70% after vaccination in one case and from 50% to at least 90% in the other. In vaccinated C3H mice challenged with a nonlethal T. gondii dose, the number of brain cysts was significantly lower than in controls. DNA vaccination did not protect BALB/c or C57BL/6 mice. Our results demonstrate for the first time in an animal model a partially protective effect of DNA vaccination against T. gondii. 相似文献
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Irradiated C57BL/6(B6) mice, when they were injected with spleen cells of C57BL/6J-lpr/lpr(B6-lpr) mice, developed splenomegaly at 2 weeks post-transfer, but afterward displaced by GVH-like disease. At 2 weeks the enlarged spleen in the chimeric mice, designated as [B6-lpr----B6] chimera, contained about 70% of the total cell population as CD8-positive T cells. Spleen cells from [B6-lpr----B6] chimeras were unresponsive to Con A and LPS stimulation and suppressed the mitogenic response of B6, B6-lpr, and C3H spleen cells to Con A. However, they had no cytotoxic activity towards Con A blasts of B6 and B6-lpr spleen cells. The suppressor activity found in the [B6-lpr----B6] spleen cells was removed by pretreatment of them with anti-Thy-1.2 or anti-CD8(Lyt2.2) plus complement. The present experiment showed that enormous proliferation of CD8-positive suppressor T cells was induced in the [B6-lpr----B6] chimeras. These cells were probably responsible for the GVH-like lymphoid atrophy observed in these [B6-lpr----B6] chimeras. 相似文献
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Marimo Sato Kenji Iwakabe Akio Ohta Masashi Sekimoto Shuichi Kimura Takashi Nishimura 《Immunology letters》2000,70(3):173-178
To monitor genetically-controlled cytokine-producing ability in mice in vitro, we developed a high-density cell culture system, which is preferable for inducing CD4+ T cell-dependent self-priming responses without any antigenic stimulation. When BALB/c spleen cells were cultured at high density (over 1.0×107 cells/well) in 12-well culture plate, they spontaneously produced cytokines including IFN-γ, IL-2, IL-3, IL-5 and IL-6. The spontaneous cytokine production in this self-priming cell culture (SPCC) system was totally dependent on MHC class II-restricted CD4+ T cells. It was demonstrated that Th2-type BALB/c background mice exhibited higher levels of spontaneous cytokine production in SPCC culture compared with Th1-type C57BL/6 mice. Moreover, using BALB/c×C57BL/6 F1 mice and B10D2 congenic mice, it was demonstrated that highly spontaneous cytokine-producing ability in BALB/c background is genetically dominant and it is controlled by non-MHC genes. Unexpectedly, BALB/c mice spontaneously produced higher levels of IL-2 and IFN-γ than C57BL/6 mice. However, BALB/c mice revealed lower levels of CTL and NK cell-generation in SPCC system compared with C57BL/6 mice. These results suggested that genetically-controlled predisposition of BALB/c mice toward Th2 immunity appeared not to be derived from their poor IFN-γ-producing ability but rather derived from their poor responsiveness to IFN-γ. 相似文献