酮替酚对鸡蛋过敏特应性皮炎患儿淋巴细胞增殖反应的抑制作用

作者探讨了鸡蛋过敏特应性皮炎(AD)患儿外周血单个核细胞(PBMCs)对卵白蛋白(OA)刺激的增殖反应并观察了酮替酚(KF)对此反应的影响.结果提示AD患儿的PBMCs增殖反应显著高于健康儿童;KF可剂量依赖性地抑制鸡蛋过敏AD患儿PBMCs对OA刺激的增殖反应,且这一效应可通过KF抑制T细胞的作用而得以实现.KF对植物血凝素(PHA)和破伤风类毒素(TT)诱导的PBMCs增殖反应无抑制作用.这说明KF只抑制食物过敏AD患者PBMCs对食物抗原的特异性增殖反应.     

Pregnancy-Associated Uterine Granulated Metrial Gland Cells in Mutant and Transgenic Mice

PROBLEM: Granulated metrial gland (GMG) cells are pregnancy-specific uterine lymphocytes found in rodents. The lineage relationships of GMG cells are incompletely defined, although genetic and immunophenotyping studies suggest membership in the natural killer (NIC) cell lineage. Pregnancy-specific functions have been postulated for GMG cells, but no successful depletion of these cells has been achieved that would permit assessment of any critical roles that might influence gestational outcome. METHOD: Routine histological methods for light microscopy were used to assess implantation sites from wild-type mice and mice of the following genotypes: tgE26, mi/mi, and p53 knockout. RESULTS: GMG cells are transient, histamine-negative cells found in the pregnant uteri of most mice. Pregnancies in the NK and T-cell-deficient tgE26 were characterized by infrequent GMG cells, very small placentae, and an elevated rate of fetal and perinatal mortality. In term placentae of mi/mi with dystocia, GMG cells were found in a new location along the plane of placental separation, and they appeared degranulated. A normal life-history was observed for GMG cells in p53 knockout mice. CONCLUSION: Pregnancies in mutant and transgenic mice indicate that GMG cells are natural killer cells and have critical roles in placental development and pregnancy success. The disappearance of GMG cells at term is independent of p53 gene expression.     

Replacement of immunoglobulin receptors by lymphocytes contained in the mouse spleen at the peak of the primary immune response

Spleen cells obtained from mice on the fifth day after injection of sheep's red cells (SRBC) irreversibly lose 50% of their surface immunoglobulin receptors during culture in vitro for 4 h. On incubation of spleen cells obtained on the ninth day after injection of the antigen no changes were observed in the total quantity of surface immunoglobulins. Metabolism of the antigen-binding receptors of immune splenic lymphocytes was studied by rosette formation. Culture of spleen cells obtained on the fifth day after injection of SRBC for 20 h showed that 70% of the rosette-forming cells (RFC) were lost. The remaining RFC belonged to -positive lymphocytes. The half-replacement time of their antigen-binding receptors was approximately 4 h. Replacement of receptors of RFC in the mouse spleen on the ninth day after antigenic stimulation takes place at the same rate. During culture of spleen cells for 20 h no decrease in the number of RFC was observed. It is postulated that the decrease in the number of RFC obtained at the peak of the primary immune response may be the result of inability of the immune lymphocytes to synthesize new receptors or the result of blocking the newly formed receptors by a soluble factor produced by immune lymphocytes during culture in vitro.N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. V. Baroyan.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 574–576, May, 1977.     

IL-15 and IL-15Rα gene deletion: Effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy

IL-15 is a potent T cell chemoattractant, and this cytokine and its unique α subunits, IL-15Rα, can modify immune cell expression of several T cell chemokines and their receptors. Facial nerve axotomy in mice leads to T cell migration across an intact blood–brain-barrier (BBB), and under certain conditions T cells can provide neuroprotection to injured neurons in the facial motor nucleus (FMN). Although chemokines and chemoattractant cytokines are thought to be responsible for T cell migration to the injured cell bodies, data addressing this question are lacking. This study tested the hypothesis that T cell homing to the axotomized FMN would be impaired in knockout (KO) mice with the IL-15 and IL-15Rα genes deleted, and sought to determine if microglial responsiveness and motoneuron death are affected. Both IL-15KO and IL-15RαKO mice exhibited a marked reduction in CD3⁺ T cells and had fewer MHC2⁺ activated microglia in the injured FMN than their respective WT controls at day 14 post-axotomy. Although there was a relative absence of T cell recruitment into the axotomized FMN in both knockout strains, IL-15RαKO mice had five times more motoneuron death (characterized by perineuronal microglial clusters engulfing dead motoneurons) than their WT controls, whereas dead neurons in IL-15KO did not differ from their WT controls. Further studies are needed to dissect the mechanisms that underlie these observations (e.g., central vs. peripheral immune contributions).     

Cytotoxic effector cells against HLA antigens in strong linkage disequilibrium: identification of a strong,new, CML determinant

Three sets of cytotoxic effector cells were generated against the A1, B8, DR3 haplotype using haptoidentical individuals in three different families. The three sets of effector cells generated against this haplotype showed excellent reproducibility testing, strong cytotoxicity against their specific targets, low autologous kill, and segregation with the sensitizing haplotype within the family. When tested against a panel of cells bearing all combinations the A1, B8. DR3 antigens, a hierarchy of contribution of the individual HLA antigens as CML target determinants was seen. A new strong target cell determinant was identified by cytotoxicity with one of the effector cells not explicable in terms of the A1, B8, DR3 antigens or known HLA cross-reactivity. A family study demonstrated that this determinant clearly segregates with HLA. The success of this approach in defining new CML determinants may result from the generation of effector cells across a single haplotype in strong linkage disequilibrium or from the presentation of CML determinants in the context of self.     

Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions

Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56- conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3-CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Valpha24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56- T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0.715, P < 0.0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56- lymphocytes and both Knodell score (r = 0.624, P = 0.003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56- conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations:     

Induction of IL-15 by TCR/CD3 aggregation depends on IFN-gamma and protects against apoptosis of immature thymocytes in vivo

TCR/CD3 aggregation by injection of anti-CD3 Ab produces T cell activation, release of cytokines such as IFN-gamma, and apoptosis in the cortical region of the thymus. We show that anti-CD3 Ab induces IL-15 mRNA in spleens of wild-type but not IFN-gamma receptor-knock-out (IFN-gammaR KO) mice. The loss of IL-15 mRNA induction in IFN-gammaR KO mice was associated with increased thymocyte apoptosis. Pretreatment of wild-type mice with neutralizing anti-IL-15 Ab increased the anti-CD3-triggered thymocyte apoptosis, thus mimicking the sensitive phenotype of IFN-gammaR KO mice. Inversely, anti-CD3-induced apoptosis in IFN-gammaR KO mice was suppressed by administration of recombinant IL-15. In IFN-gammaR KO mice and in wild-type mice that were treated with anti-IL-15, augmented apoptosis affected mainly CD4+CD8+ immature thymocytes. IL-15 as well as IL-15Ralpha mRNA expression in thymocytes was not increased by anti-CD3. These data demonstrate that systemic IL-15 exerts anti-apoptotic activity on immature T cells and establish a regulatory mechanism whereby TCR/CD3 engagement induces IL-15 expression via an IFN-gamma-dependent pathway. The self-amplifying nature of this IFN-gamma/IL-15 connection may constitute a regulatory pathway in central tolerance to self.     

人乳头状瘤病毒11型E7抗原HLA-A*0201限制性细胞毒性T淋巴细胞表位的功能鉴定

目的 筛选和鉴定人乳头状瘤病毒11型E7抗原(HPVllE7)HLA-A*0201限制性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位.方法 预测HPVllE7抗原HLA-A*0201限制性CTL表位并合成相对应的表位多肽和四聚体(tetramer),即HPVllE7 7-15(TLKDIVLDL)、15-23(LQPPDPVGL)、47-55(PLTQHYQIL)、81-89(DLLLGTLNI)和82-90(LLLGTLNIV).从健康HLA-A*0201成人外周血单一核细胞诱导树突状细胞(DC)并负载上述表位多肽,流式细胞技术检测DC成熟分化标记及ELISA法检测DC分泌的IL-12;成熟DC负载各组多肽后观察DC激活T淋巴细胞的效应,ELISA法检测T细胞分泌的IFN-γ;四聚体检测抗原特异性CD8+ T细胞及乳酸脱氢酶(LDH)释放法评价DC诱导的CTL对靶细胞的特异性体外杀伤效应.结果 预测的5条HPVllE7表位多肽均能诱导DC的成熟分化;E7 7-15、82-90和15-23多肽负载的DC能激活T淋巴细胞分泌高水平IFN-γ;E7 7-15多肽负载的DC能刺激特异性tetramer+CD8+细胞增殖且其诱导的CTL对HPVllE7/293细胞产生高效率的特异性杀伤作用(P<0.05).结论 筛选并鉴定出1条HPVllE7HLA-A*0201限制性CTL表位E7 7-15(TLKDIVLDL),负载该表位肽的DC体外可诱导高效、特异性的CTL效应,抗原性较强,有可能作为HPV感染治疗用肽疫苗的候选表位.     

Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes

Using an 'oligoclonal' model, we have previously shown that mice transgenic for a mu chain (H3) and deficient for kappa chain expression display a mature B cell repertoire largely dominated by the H3/lambda1 pair, while the four H3/lambda available combinations can be observed in the immature B cell compartment. This led us to propose the existence of a positive selection process. To test this hypothesis, we have introduced the SJL lambda locus coding for a defective lambda1 chain (lambda1(s)) that creates a dysfunctional Ig receptor complex during B cell differentiation. Our results show that the lambda1(s) defect impairs the development of mature B cells when the H3-mu transgene insert is present in the hemizygous state. This suggests that the Gly --> Val substitution present in the C(lambda)1(s) chain at position 155 is sufficient to abrogate the selection of the H3/lambda1 pair. Unexpectedly, when the H3-mu transgene array is present in a homozygous state in lambda1(s) mice but not in 'wild-type' lambda1 mice (lambda1(+)), a significant number of mature B cells expressing all H3/lambda combinations can be developed. These results indicate that the overriding H3/lambda1 dominance observed in lambda1(+) mice is due to a positive selection process and not to a negative selection of other H3/lambda combinations. They also show that the export of B cells to the periphery can be controlled by the expression of the mu chain.