共查询到20条相似文献,搜索用时 46 毫秒
1.
Atsumi Toru; Sato Masae; Kamimura Daisuke; Moroi Arisa; Iwakura Yoichiro; Betz Ulrich A. K.; Yoshimura Akihiko; Nishihara Mika; Hirano Toshio; Murakami Masaaki 《International immunology》2009,21(1):73-80
Infection with pathogens containing superantigens (Sags) canresult in massive excessive CD4+ T cell activation and deathin such conditions as toxic shock, food poisoning and autoimmunediseases. We here showed how enhancement of IL-6 signaling suppressesSag-mediated activated CD4+ T cell death. Sag-induced CD4+ Tcell death increased in IL-6 knockout (KO) mice, whereas itdecreased in mice characterized by enhanced IL-6–gp130–STAT3signaling. The serum concentration of IFN- was inversely correlatedwith the magnitude of IL-6 signaling, and IFN- deficiency inhibitedSag-induced activated CD4+ T cell death, suggesting that IL-6suppresses CD4+ T cell death via IFN- expression. Interestingly,depletion of activated CD8+ T cells inhibited Sag-mediated increasesin IFN- expression in IL-6 KO mice as well as the augmentedCD4+ T cell death. The results demonstrate that IL-6–gp130–STAT3signaling in activated CD8+ T cells contributes to Sag-inducedCD4+ T cell death via IFN- expression, highlighting this signalingaxis in CD8+ T cells as a potential therapeutic target for Sag-relatedsyndromes. 相似文献
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Emigration of selected subsets of {gamma}{delta}+ T cells from the adult murine thymus 总被引:1,自引:0,他引:1
Kelly Katherine A.; Pearse Martin; Lefrancois Leo; Scollay Roland 《International immunology》1993,5(4):331-335
Cells bearing the form of the TCR make up only 1–3% ofT cells in the adult murine thymus and peripheral lymphold organs.Evidence from studies of nude mice suggests that the developmentof at least some T cells is thymus dependent; however, untilnow it has not been directly demonstrated that cells are exportedfrom the thymus. In this paper we have used the technique oflabelling thymocytes in vivo with FITC, followed by flow cytometrlcanalysis to trace cells emigrating from the thymus to the spleen.Using this approach we have been able to demonstrate for thefirst time that T cells are exported from the adult murinethymus to the spleen. We also demonstrate that the cells emigratingto the spleen are a selected subset of thymocytes being heatstable antigen positive, Thy-1+, and expressing low levels ofCD44 (Pgp-1). In addition, investigation of TCR V; gene usageamong adult + thymocytes, recent emigrants, and spleen cells,indicated a selective emigration of cells expressing certainVgenes. 相似文献
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Predominant expression of invariant V{alpha}14+ TCR {alpha} chain in NK1.1+ T cell populations 总被引:5,自引:0,他引:5
Makino Yasuhiko; Kanno Rieko; Ito Toshihiro; Higashino Kazuko; Taniguchi Masaru 《International immunology》1995,7(7):1157-1161
A novel T cell subset characterized by cell surface NK1.1+ TCRß+expression was investigated for its TCR usage, particularlythat of invariant V14 TCR, which was found to be preferentiallyused in peripheral CD4–CD8–T cells developed atextrathymic sites. We found that NK+ ß T cell subsetsaccount for 0.4% in thymocytes, 5% in the splenic T cells and40.5% in the bone marrow T cells. Among these NK+ ßT cells, two distinct subsets were detected; cell surface TCRV14+and V14– subpopulations. Almost all of NK+ ßthymocytes express V14 mRNA; however, only<20% were positive,while >80% were negative or undetectable for V14 TCR expressionon the cell surface in the thymus. Similarly,50% of NK+ ßT cells in spleen and bone marrow are V14+; as revealed by FACS.TCR repertoire analysis by nucleotide sequences on inverse PCRproducts demonstrated that most NK+ ß T cells expressan invariant TCR encoded by the V14J281 gene with a 1 base N-regionin all tissues. Thus, invariant V14 TCR is uniquely expressedon NK T cells, and can be a marker to distinguish NK, NK T andT cells. 相似文献
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Ohno Hiroshi; Aoe Tomohiko; Ra Chisei; Yamamoto Tadashi; Saito Takashi 《International immunology》1993,5(11):1403-1411
The structure and function of the TCR-CD3 complex containinga homodimer of the gamma chain of the high affinity receptorfor IgE (FcR) (FcR+ TCR) was investigated by transfecting theFcR gene into a CD3–, CD3–, FcR– T cell line.Introduction of FcR, as well as CD3, induced a high expressionof the TCR-CD3 complex on the cell surface. Transfected FCRformed a homodimer and associated firmly with the TCRßdimer but only weakly with the CD3. Stimulation of both FcRand CD3 transfectants by antibodies against TCR or CD3 inducedaccumulation of inositol phosphates, the Ca2+ response, IL-2production, and growth inhibition. On the other hand, antigenstimulation of transfectants expressing FcR as well as CD3 inducedIL-2 production, but only the latter exhibited the antigen-inducedgrowth inhibition. In vitro kinase assay suggested that theCD3 dimer but not the FcR dimer associates with the Fyn kinase.These results indicate that the FcR homodlmer Is able to forma functional TCR complex but that the mode of assembly and thesignaling function of FcR+ TCR, including its association withtyrosine klnase(s), may differ from the TCR-CD3 complex containingCD3 homodimers (+ TCR). This provides an example which illustratesthat different TCR isoforms mediate distinct signals and functions. 相似文献
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Molecular studies of the TCR, which is expressed by a minorsubpopulatlon of T lymphocytes in all vertebrate species, havedefined a subset which expresses a receptor with extreme junctionaldiversity and a second subset, most commonly found in eplthella,which expresses a receptor of very limited diversity. In thedeveloping murine thymus, T cells appear in an ordered sequenceof specific v rearrangements, V3V, 1 on day 14, V2V1 on day17, and subsequently V4V5, V6, or V7. We demonstrate that thetransfer of expanded populations of cells from newborn thymusand cell lines expressing the invariant V3V1 receptor into SCIDmice, which lack T and B cells, results in the appearance ofCD3–CD4+CD8+ thymocytes. Thus, one role of the early appearingV3V1 T cells in thymlc development in vivo is to promote CD4and CO8 surface expression on precursor cells. 相似文献
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Herpesvirus saimiri immortalization of {alpha}{beta} and {gamma}{delta} human T-lineage cells derived from CD34+ intrathymic precursors in vitro 总被引:1,自引:0,他引:1
Pacheco-Castro Alberto; Marquez Carlos; Toribio Maria L.; Ramiro Almudena R.; Trigueros Cesar; Regueiro Jose R. 《International immunology》1996,8(11):1797-1805
Herpesvirus saimiri (HVS), an agent that can infect many humancell types, has been shown to immortalize selectively TCR ß+CD3+T lymphocytes. Human T cell precursors defined as CD34+CD3–CD4–CD8–were isolated from thymic samples and exposed to HVS in thepresence of either IL-2 or IL-7. Cultures lacking the viruswere non-viable by day 15. Test cultures, in contrast, showeda sustained proliferative activity lasting >5 months, allowingthe phenotypical and molecular analysis of the cellular progeny.In the presence of IL-7, TCR ß+ cells with three differentphenotypes (mainly CD4+CD8–, but also CD4+CD8+ and CD4–CD8+)were immortalized, whereas no TCR + cells were recovered. Kineticstudies showed that the expansion of immortalized TCR ß+cells was preceded by a gradual loss of CD34+ cells followedby a transient accumulation of two distinct cell subsets: firstCD1+CD4+CD3– cells and then CD4+CD8+ thymocytes. Thisresembles early phenotypic changes occurring during normal intrathymicT cell development. In the presence of IL-2, in contrast, onlyTCR + cells were immortalized (mainly CD4–CD8+, but alsoCD4–CD8–). The results show that HVS can be usedto read the CD3+ cellular outcome of T cell differentiationassays, including + CD4–CD8+, +CD4–CD8–, ß+CD4+CD8–,ß+CD4–CD8+ and ß+CD4+CD8+ T cells.A clear role for different cytokines (IL-2 for + cells, IL-7for ß+ cells) in early T cell commitment was alsoapparent. 相似文献
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Hansch Holger C. R.; Smith Debbie A.; Mielke Martin E. A.; Hahn Helmut; Bancroft Gregory J.; Ehlers Stefan 《International immunology》1996,8(8):1299-1310
Infection with the virulent Mycobacterium avium strain TMC 724caused progressive Infection in C57BL/6 and BALB/c mice, whileinfection with a less virulent strain (M. avium SE 01) resultedIn chronically persistent bacterial loads. Livers of mice Infectedwith TMC 724 were characterized by progressively expanding tumor-likeInfiltrations of epithelloid macrophages, while SE 01 Inducedwell-developed, compact epithelioid granulomas that remainedconstant in size and number for at least 4 months. When C57BL/6mice were depleted of CD4+ T cells by i.p. administration ofspecific mAb at the time of infection, their capacity to Initiategranuloma formation was completely abrogated during the first4 weeks of infection. Semi-quantltatlve competitive RT-PCR ofliver homogenates obtained 3 weeks after infection revealedthat depletion of CD4+ T cells was accompanied by a 25-foldreduced expression of IFN- mRNA and a 5-fold reduced expressionof tumor necrosis factor (TNF)- mRNA when compared to controlInfected mice. Granuioma morphology in response to either TMC724 or SE 01 was similar in immunodeficlent SCID mice to thatobserved In syngeneic BALB/c mice. However, SCID mice developedgranuiomas In a delayed fashion and were less efficient in surroundingInfected Kupffer cells with an inflammatory infiltration. Thedelayed kinetics of granuioma Initiation In Infected SCID micewas paralleled by a lower mRNA expression for IFN- and TNF-compared to that observed in Infected BALB/c mice. mAb-mediatedneutralization of IFN- In BALB/c mice significantly reducedinflammatory infiltrations and granuioma formation. These datasupport the conclusion that CD4+ T cells accelerate granuiomaformation by enhancing the production of TNF- and IFN- at thesite of infection. 相似文献
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CD2 expression on murine intestinal intraepithelial lymphocytes is bimodal and defines proliferative capacity 总被引:1,自引:0,他引:1
Van Houten Nancy; Mixter Philip F.; Wolfe Julie; Budd Ralph C. 《International immunology》1993,5(6):665-672
The CD2 molecule is normally expressed on nearly all murinelymphocytes, and is co-stimulatory in T cell activation viathe antigen receptor (TCR). A naturally occurring T lymphocytepopulation that is bimodal for CD2 expression was found in theintestinal intraepithelial lymphocytes (IEL). TCRß+IEL contain CD2– and CD2+ cells of approximately equalproportion, while TCR+ IEL are predominantly CD2–. Theproliferative response of IEL to stimulation with an anti-CD3mAb or with PMA plus ionomycin co-segregated with CD2 expression;the CD2+ subset proliferated vigorously under these conditionswhile the CD2– subset was much less responsive. The respondingCD2+ IEL contained both TCRß+ and TCR+ cells. However,activation of the CD2– IEL with anti-CD3 mAb resultedin only the expansion of TCR+ IEL, while activation with PMAplus ionomycin did not promote expansion of either the TCRß+or the TCR+ IEL. These findings parallel observations in theautoimmune lpr mouse, where massive numbers of peripheral TCRß+CD4–CD8–T cells that lack CD2 expression are also hyporesponsive tomltogenic stimulation. The apparent energy of CD2–TCRß+IEL, as well as CD2– T cells from lpr mice, demonstratesthat the absence of CD2 on TCRß+ T lymphocytes co-segregateswith nonresponsiveness. 相似文献
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Induction of IFN-{gamma} in macrophages by lipopolysaccharide 总被引:9,自引:0,他引:9
Fultz Marion J.; Barber Sheila A.; Dieffenbach Carl W.; Vogel Stefanie N. 《International immunology》1993,5(11):1383-1392
In this paper we report that macrophages can be stimulated toexpress detectable levels of IFN--specific mRNA. Macrophagesfrom lipopolysaccharide (LPS)-responsive, C3H/OuJ mice are inducedby LPS to increase steady-state levels of IFN--specific mRNA,while those from LPS-hyporesponsive C3H/HeJ mice are not. Thisinterstrain variation is apparently the result of LPS-specificsignal differences since macrophages derived from both Lpsnand Lpsd mouse strains are able to produce comparable levelsof IFN--specific mRNA following stimulation with polyinosinic-polycytidylicacid. The identity of the cell type responsible for this IFN-message appears to be the macrophage as IFN--specific mRNA wasalso detectable following T and natural killer cell depletion,in the LPS-stimulated RAW 264.7 cell line, and in a homogeneouspopulation of mature macrophages propagated in vitro by stimulationof bone marrow progenitors with recombinant colony stimulatingfactor-1. Immunofluorescent staining of fixed and permeabilizedLPS-stimulated macrophages confirmed the presence of immunoreactiveIFN- protein. The possible significance of IFN- production bymacrophages is discussed in the context of normal macrophagedifferentiation as well as the inflammatory immune response. 相似文献
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Balk Steven P.; Polischuk John E.; Probert Christopher; Stevens Christopher; Ebert Ellen; She Jian; Terhorst Cox; Blumberg Richard S. 《International immunology》1995,7(8):1237-1241
Human intestinal intraepithelial lymphocytes (DEL) are a uniquepopulation of predominantly CD8ß+ TCRß+lymphocytes and, to a lesser extent, TCR+ lymphocytes that proliferatepoorly to anti-CD3 mitogenic signals but display significantcytolytic activity. Studies in mouse model systems have shownthat the chain of the high-CD3 affinity receptor for IgE (FcRl)may substitute for the chain in the TCR-CD3 complex of iIEL.This has suggested that the functional properties of these cellsmay be associated with an altered composition of the TCR-CD3complex. We therefore analyzed the TCR-CD3 complex of normalhuman iIEL. One-and two-dimensional non-reducing/reducing SDS-PAGEanalysis of CD3, CD3, CD3, and FcRr chain immunopreclpitatesof cell surface radiolabeled proteins with subunit-specificantibodies revealed a TCR-CD3 complex without associated FcRrchains. Thus, normal human NEL contain a TCR-CD3 complex thatconsists predominantly of , homodimers in association with theß TCR and CD3, and , similar to the majority of peripherallymphocytes. This indicates that the distinct properties ofhuman DEL are not associated with substitutions of the FcRlchain in the TCR-CD3 complex. 相似文献
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The development of dermatitis infiltrated by {gamma}{delta} T cells in IL-7 transgenic mice 总被引:3,自引:0,他引:3
Uehira Masahiro; Matsuda Hidetoshi; Hikita Ichiro; Sakata Tsuneaki; Fujiwara Hiromi; Nishimoto Hirofumi 《International immunology》1993,5(12):1619-1627
Transgenic mice constitutively expressing IL-7 developed severedermatitis with erythroderma and alopecia. The skin lesionswere characterized by massive infiltration of mononuclear cells.Immunofluorescence staining showed that most of the infiltratingcells were T cells with the majority bearing the TCR otherthan the V5 moiety. Furthermore, the number of T cells hadincreased in the lymphold organs of the dermatitis animals.These findings idicate the strong relationship between the expressionof IL-7 and the development of T cells in vivo and the pathologicalinvolvement of proliferated and/or activated T cells in skindisease. 相似文献
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Zou Jian-Ping; Yamamoto Norihiko; Fujii Tetsuya; Takenaka Hiroshi; Kobayashi Michiko; Herrmann Steven H.; Wolf Stanley F.; Fujiwara Hiromi; Hamaoka Toshiyuki 《International immunology》1995,7(7):1135-1145
Unfractionated spleen cells taken from tumor-bearing mice 2weeks after tumor implantation contained tumor-primed T cellswhich produced cytokines including IL-2 and IFN- when culturedin vitro. With progressive tumor growth this initial lymphokine-producingcapacity decreased. Here, we investigated the ability of IL-12to (I) restore suppressed IFN- production, (II) cause tumorregression and (II) induce anti-tumor protective immunity. Additionof rIL-12 to spleen cell cultures from 4- to 10-week-old tumor-bearingmice resulted in a striking enhancement in the production ofIFN- compared with cultures of these cells in the absence ofrIL-12 or of normal spleen cells in the presence of rIL-12.Five I.p. injections of rIL-12 into mice bearing s.c. tumorsinduced complete tumor regression. This was found when rIL-12was given at early (1–2 weeks), intermediate (4–5weeks) or even late (7 weeks) stages of tumor growth. Furthermore,IL-12-treated mice which rejected the primary tumor exhibitedcomplete resistance to a rechallenge with the same tumor butdid not reject a second syngenetic tumor. Immunohistochemicalanalyses following IL-12 treatment revealed that CD4+ and CD8+T cells infiltrate the tumor. More importantly, IFN- mRNA expressionwas observed in fresh tumor masses from tumor-bearing mice receivingIL-12 treatment The importance of IFN- was further demonstratedby the observation that the systemic administration of anti-IFN-mAb prior to IL-12 treatment completely abrogated the anti-tumoreffect of IL-12. Thus, these results indicate that administrationof modest levels of rIL-12 to tumor-bearing mice results intumor regression through mechanisms involving reversal of suppressedIFN- production by anti-tumor T cells and the establishmentof a tumor-specific protective immune response. 相似文献
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Bovine {gamma}{delta} T cells express high levels of functional peripheral lymph node homing receptor (L-selectin) 总被引:1,自引:0,他引:1
Lymphocyte migration from the blood into specific tissues Isdirected by their expression of adhesion molecules referredto as homing receptors. The homing receptor L-selectln, forexample, directs the migration of lymphocytes into peripherallymph nodes (PLN). Since bovine T cells, a major lymphocytesubset in peripheral blood (25–50%), represent only aminor subset in PLN, we examined whether these cells lack expressionor function of L-selectin. We found that bovine T cells expressedL-selectln at levels higher (2- to 5-fold) than ßT cells and B cells. Furthermore, T cells accumulated alongthe vascular wall of venules that support lymphocyte extravasationinto PLN (MECA-79+ venules) in vivo and bound mouse PLN highendothelial cell venules in an In vivo binding assay. In contrastto this primary adhesive event, we directly demonstrate that T cells in vivo do not appreciably extravasate from the bloodinto the parenchyma of lymph nodes. Since the lack of functionalL-selectln expression could not account for the inability of T cells to enter PLN, we tested for other differences between T cells and PLN homing lymphocytes related to the processesfollowing primary adhesion; for instance, the down-regulationof L-selectin expression following short-term activation andthe expression of accessory adhesion molecules necessary fortransendothellal migration. We found that and ß Tcells demonstrate differential down-regulation of L-selectinafter PMA activation. Kinetic analysis revealed that, at alltime points after PMA treatment, L-selectin expression remainedsignificantly higher on T cells and was down-regulated at aslower rate compared with ß T cells. However, theexpression levels of CD44 and CD18 on and ß T cellswere found to be equivalent. This study Is the first to demonstratefor lymphocytes that the expression of L-selectln alone doesnot predict a PLN homing capacity. Our results suggest thatthe T cells' reduced ability to enter PLN may be due to inefficientdown-regulation of L-selectln compared with non- lymphocytes,thus potentially disrupting the dynamics of the extravasationevent. 相似文献
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Uehara Shoji; Hitoshi Yasumichi; Numata Fumio; Makino Masahiko; Howard Maureen; Mizuochi Toshiaki; Takatsu Kiyoshi 《International immunology》1994,6(12):1937-1947
The murine acquired immunodeficiency syndrome (MAIDS) causedby a defective murine leukemia virus produces severe immunodeficiencywith abnormal lymphoproliferation and hypergammaglobulinemia.The presence of both CD4+ T cells and B cells is critical forthe development of this disease. Remarkably elevated mRNA expressionfor IFN- and IL-10 was observed in spleen cells of C67BU6 micestarting from the early phase of viral infection. IFN- productionwas induced by spleen cells from virus-infected mice upon stimulationwith concanavalln A or lipopolysaccharide in both the earlyand late phases of MAIDS progression. When mice that had beenpassively administered anti-IFN- mAb were infected with thevirus, the development and progression of lymphadenopathy, immunodeficiencyand elevated levels of serum lgG2a associated with MAIDS weredelayed. Treatment with anti-IL-4 or anti-IL-10 mAb in placeof anti-IFN- mAb did not induce the delayed progression of MAIDS.These data support the concept that IFN--dependent pathway maybe involved in the development of MAIDS. 相似文献
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A pivotal role of IL-12 in Th1-dependent mouse liver injury 总被引:5,自引:0,他引:5
Tanaka Yoshitaka; Takahashi Akiko; Watanabe Kazuhito; Takayama Kiyoshi; Yahata Takashi; Habu Sonoko; Nishimura Takashi 《International immunology》1996,8(4):569-576
Intravenous injection of Proplonibacterium acnes and llpopolysaccharide(LPS) with a 7 day interval caused CD4+ T cell-dependent severeliver injury in the C57BL/6 (H-2b) mouse strain. In contrast,BALB/c (H-2d mice were resistant to P. acnes and LPS-inducedliver injury. The different susceptibilities of the two mousestrains to liver injury appeared to be closely correlated withtheir different abilities to produce IFN- after P. acnea priming.Namely, the sensitive C57BL/6 mouse strain produced a significantlevel of IFN- 7–10 days after P. acnes injection, whereasno significant amount of serum IFN- was detected in the resistantBALB/c mouse strain. The important role of IFN- in liver injurywas demonstrated from the finding that In vivo administrationof anti-IFN- mAb abrogated P. acnes and LPS-induced liver injuryin C57BL/6 mice. Moreover, it was demonstrated that In vivoadministration of recombinant IL-12, a key cytokine for theinduction of IFN-, into mice induced P. acnes and LPS-inducedliver injury in the resistant BALB/c mouse strain. Conversely,In vivo administration of anti-IL-12 mAb blocked the developmentof liver injury in the sensitive C57BL/6 mouse strain. Moreover,it was demonstrated that the failure of the induction of liverinjury in BALB/c mice appeared to be derived from the lack ofexpression of IL-12 at the local site of liver in P. acnes-prlmedmice. These results strongly indicated that endogenous IL-12,which stimulates Th 1-dominant cellular immunity and IFN- production,may be an essential cytokine on the course of T cell-dependentliver injury. 相似文献