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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
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We have previously found that T ceILs from mice bearing plasmaceIL tumors (PCT mice) demonstrate decreased proliferation asweIL as decreased production of the Th 1-associated cytokinesIL-2 and IFN- in response to polyclonal stimulation. In thepresent study, we have examined soluble factors as possibleelements required to rescue this decreased proliferation andcytokine production by splenocytes from PCT mice. We find thatthe addition of supernatants from stimulated normal splenocyteshas no effect on proliferation or IL-2 production by splenocytesfrom PCT mice. In contrast, these supernatants completely restoreIFN- production by splenocytes from PCT mice. We have foundthat IL-12 is responsible for the observed increase in IFN-production because: (i) addition of anti-IL-12 antibody blocksthis recovery of IFN- production by these supernatants, (ii)the addition of recombinant IL-12 to cultures of splenocytesfrom PCT mice results in increased IFN- production and (iii)In vivo treatment of PCT mice in IL-12 also results in increasedIFN- production by the subsequently activated splenocytes, buthas little effect on proliferation or IL-2 production. Theseresults demonstrate that both in vitro and in vivo, IL-12 selectivelyrestores the decreased production of IFN- by splenocytes fromPCT mice. 相似文献
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Yu Wen-Gong; Yamamoto Noriniko; Takenaka Hiroshi; Mu Jie; Tai Xu-Guang; Zou Jian-Ping; Ogowa Makoto; Tsutsui Tateki; Wijesuriya Rishani; Yoshida Ryotaro; Herrmann Steven; Fujiwara Hiromi; Hamaoka Toshiyuki 《International immunology》1996,8(6):855-865
The present studnt Investigates the molecular by which IFN-produced as a result of in vitroIL-12 addministration exertsits anty-tumor,rIL-12 was administered three or five times intomice bearing CDA1M fibrosarcoma, OV-HM ovarian carcinoma orMCH-1-A1 fibosarcoma. This regimen induced complete regressionof CSA1M and OV-HM tumors but only transient growth inhibitionof MCH-1-A1 tumors. The anty-tumor effects of Il-12 were associatatedwith enhanced induction of IFN-becouse these effects were abrogatedby pretreatment of hosts with anti-IFN- antibody.Exposure inin vitro of the three types of tumor cells to rIFN- resultedin moderate to potent inhibition of tumor cell growth.IFNstimulatedthe expression of mRNAs for an inducible type of NO synthasa(INOS)in CSA1M cells and indoleamine 2,3-dioxygenasa (IDO),an enzyme capable of degrading tryptophan, in OV-HM cells ,but induced only marginal levels of these mRNAs in MCH-I-ALcells. In association withiNOS gene expression, INF--stimulatedCSA1M cells produced a large amount of NO which functioned toinhibit their own growth in vitro. Although OV-HM and MCH-1-A1cells did not produce NO, they also exhibited NO susceptibility.Whereasthe tumor masses from IL-12-treated CSA1M-bearing mice inducedhigher levels of INOS (for CSA1M) or IDO and iNOS (for OV-HM)mRNAs,the MCH-1-A1 tumor mass expressed lower levels of iNOS mRNAalone.Moreover, massive infiltration of CD4+and CD8+ T cellsand Mac-1+ cells was seen only in the CSA1M and OV-HM tumors.Thus, these results indicate that IFN- produced after IL-12treatment induces the expression of various genes with potentialto modulate tumor cells and growth by acting directly on tumorecells or stimulating tumor-infiltrating lymphold cells and thatthe effectiveness of IL12 therapy is assoiated with the operation if these mechanisms. 相似文献
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Christensen Jan Pravsgaard; Stenvang Jens Peter; Marker Ole; Thomsen Allan Randrup 《International immunology》1996,8(9):1453-1461
Infection with lymphocytic chorlomeningitis virus is associatedwith marked polyclonal activation of the CD8+ T cell subpopulation.In this report the cytokine production of virus-activated Tcells is analyzed and the producing cells subset is characterizedphenotypically. CoinciB. A. Askonasding with other parametersof cell-mediated immunity, splenic T cells appear which areable to release high amounts of IFN-, but not IL-5, IL-10 ortumor necrosis factor- upon short-term stimulation with anti-CD3in vitro. A similar profile is observed analyzing T cells takenfrom an inflammatory site. Phenotypically, the main cytokine-producingcell subset is found to be CD8+ cells targeted for homing toinflammatory sites (VLA-4hiL-selectinlo) of which 30–40%were positive by intracellular staining for IFN-. This subsetalso contains all T cells with a cytotoxic potential as measuredby redirected killing. An enhanced cytotoxic potential as wellas an increased capacity to produce IFN- is observed for atleast 2 months after infection and cell sorting analysis revealedthat this could be ascribed to a long-standing increase in thefrequency of CD8+Pgp-1hi cells. Therefore, these results demonstratethat systemic virus infection may exert marked perturbationof the CD8+ T cell population resulting in generation of a long-livedsubset of primed cells with important effector potential. 相似文献
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Administration of recombinant IL-12 to normal mice enhances cytolytic lymphocyte activity and induces production of IFN-{gamma} in vivo 总被引:19,自引:0,他引:19
Gately Maurice K.; Warrier Rajeev R.; Honasoge Sharmila; Carvajal Daisy M.; Faherty Denise A.; Connaughton Suzanne E.; Anderson Timothy D.; Sarmiento Ulla; Hubbard Brian R.; Murphy Molly 《International immunology》1994,6(1):157-167
2 Is a heterodlmerlc cytoklne that has been shown to enhancenatural killer (NK) and cytotoxic T lymphocyte (CTL) responses,and to induce IFN- production in vitro. In this study, we haveexamined the effects in vivo of administering purified murinerlL-12 to normal mice. Dally injections of riL-12 I.p. (1 ngto 10 µg/day) caused dose-dependent enhancement of NKcell lytic activity in the spleens and livers of treated mice.Histologlc examination of the livers of IL-12-treated mice revealedfocal mononuclear cell infiltrates, and flow cytometry studiesindicated that the livers of IL-12-treated mice contained increasednumbers of NK cells, CD8+ T cells, and monocytes. Liver andsplenic lymphold cells from IL-12-treated mice, unlike liverand splenic lymphoid cells from control mice, spontaneouslysecreted IFN- in vitro, suggesting that they had been inducedby IL-12 to produce IFN- in vivo. Consistent with this, IFN-could be detected in the serum of IL-12-treated mice. In micewhich had been immunized by footpad injection of allogenelcsplenocytes, dally administration of rlL-12 I.p. was shown toenhance the specific CTL response in the draining lymph nodes.Thus, these studies demonstrate that IL-12 can enhance NK andCTL activity and induce IFN- production in vivo, as well asin vitro, and suggest possible mechanisms by which IL-12 mayexert therapeutic effects in the treatment of some tu more andinfectious diseases. 相似文献
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Brucella abortus induces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-{gamma} in CD4+ T cells 总被引:7,自引:0,他引:7
Svetic Antonela; Jian Y. C.; Lu P.; Finkeiman F. D.; Gause W. C. 《International immunology》1993,5(8):877-883
Immunization of BALB/c mice with killed Brucella abortus (BA)has previously been shown to Increase serum lgG2a levels andlong-term T cell clones from these mice secrete Th1-associatedcytokines: IFN- and IL-2 but not IL-4 or IL-5. We analyzed cytokinegene expression following primary immunization with BA to determinewhen CD4+ T cells first express cytokine genes and whether specifichypothesized cytokine patterns (e.g. Th precursor, Th0) couldbe identified prior to a Th1-like pattern. Our results demonstrateda highly consistent and novel pattern of Th 1/Th2 cytokine geneexpression characterized by elevated IL-10 and IFN- in CD4+T cells which rapidly manifests itself and is sustained forat least 10 days after immunization. No elevation in IL-2 cytokinegene expression was observed and treatment of BA-immunlzed micewith blocking anti- IL-2 antibodies had no effect on the cytokinegene expression pattern, although treatment with anti-IFN antibodiesresulted in increased IL-4, IL-5, and IL-9 cytoklne gene expression,In the absence of any change In IFN- or IL-10 as early as 4days after immunization. These results suggest that a wholepathogen may trigger sufficient costimulatory signals to rapidlyinduce effector T cells in the absence of elevated IL-2 andthat IL-10 Is specifically elevated in certain Th1-like responses. 相似文献
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IL-4 producing CD4+ TCR{alpha} {beta}int liver lymphocytes: influence of thymus, {beta}2-microglobulin and NK1.1 expression 总被引:2,自引:0,他引:2
The present report describes developmental, phenotypic and functionalfeatures of unconventional CD4+ TCRß lymphocytes.In C57BL/6 mice, the majority of liver lymphocytes expressingintermediate intensity of TCRß (TCRßint)are CD4+NK1.1+ and express a highly restricted TCR Vßrepertoire, dominated by Vß8 with some contributionby Vß7 and Vß2. Although these cells expressthe CD4 co-receptor, they are present in H2-l Aß (Aß)+/–gene disruption mutants but are markedly reduced in ß2-microglobulin(ß2m)–/– mutant mice and hence are ß2mdependent. Thymocytes expressing the CD4+NK1.1+ TCR ßphenotype are also (ß2m) contingent, suggesting thatthese two T lymphocyte populations are related. The CD4+NK1.1+TCRßlymphocytes in liver and thymus share several markers such asLFA-1+, CD44+, CD5+, LECAM-1– and IL-2Rßa. TheCD4+NK1.1 + TCRßint liver lymphocytes were not detectedin athymic nuinu mice. We conclude that ß2m expressionis crucial for development of the CD4+NK1.1+ TCRßintliver lymphocytes and that thymus plays a major role. CD4+ TCRßintliver lymphocytes were also identified in NK1.1+ mouse strains,there lacking the NK1.1 marker. We assume that the NK1.1 moleculeis a characteristic marker of the CD4+TCR"int liver lymphocytesin NK1.1+ mouse strains, although its expression is not obligatoryfor their development. The liver lymphocytes from +2m+/–,but not from +2m–/–mice are potent IL-4 producersin response to CD3 or TCRß engagement and the IL-4production by liver lymphocytes was markedly reduced by treatmentwith anti-NK1.1 mAb. We conclude that the CD4+NK1.1+ TCRßintliver lymphocytes are capable of producing IL-4 in responseto TCR stimulation. 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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Utsuyama Mansanori; Albright Julia W.; Holmes Kevin L.; Hirokawa Katsuiku; Albright Joseph F. 《International immunology》1994,6(8):1107-1115
After a 3 week course (approximately), during which there ismarked lymphoid hyperplasia, Trypanosoma musculi infectionsin young-adult mice are cured by an immune mechanism involvingantibodies of the IgG2a isotype. Both the lymphoid hyperplasiaand IgG2a antibody response are T-cell-dependent events andboth processes appear to be defective in aged mice. The purposeof the studies reported here was to elucidate the effects ofT.musculi infection on subsets of T cells for two reasons: (I)to gain insight into the probable roles of selected cytokines(IL-2, IL-4 and IFN-) in facilitating the production of curative,lgG2a antibodies, and (II) to examine the hypothesis that agingaffects the competence of CD4+ T cells to participate in immunologicalcontrol of infections. The major conclusions from these studiesare that: (I) T. musculi infection of mice induces rapid changein the CD4+ T cell population toward predominance of the activatedor memory (CD45RBloCD44hi) phenotype, cells which produce IFN-,II-3. IL-4 and IL-5, accompanied by profound Inhibition of IL-2production, and (II) in the old mice these changes are superimposedon the natural age-associated changes in the same direction(i.e. toward predominance of CD45RBloCD44hi T cells).Thus, inthe old animals, the combined changes of aging and infection,moving in the same direction, are devastating, resulting inthe aged animals being unable, or barely able, to control infection. 相似文献
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Macatonia Steven E.; Hsieh Chyi-Song; Murphy Kenneth M.; O'Garra Anne 《International immunology》1993,5(9):1119-1128
We have examined the antigen presenting cell (APC) requirementsfor primary T cell activation and T helper (Th) cell phenotypedifferentiation using naive CD4+ T cells from ß TCRtransgenic mice. Purified dendritic cells were the principalcell required for induction of primary ovalbumln peptide specificT cell activation and clonal expansion. However, dendritic cellsdid not induce differentiation of T cells toward Th1 or Th2phenotype. Addition of IL-4 during primary dendritic cell stimulationsof T cells resulted in the development of a Th2 phenotype whichproduced high levels of IL-4 during secondary and tertiary stimulation.In contrast, development of Th1 cells producing high levelsof IFN- could not be induced with dendritic cells alone butrequired the addition of appropriately activated macrophages.Addition of splenic or peritoneal B cells did not induce Th1development. Activated splenic macrophages induced Th1 developmentvia a non-MHC restricted mechanism. Thus, requirements for inductionof proliferation of naive CD4+ T cells are distinct from thosedirecting Th1 phenotype development. IL-12 could replace therequirement for macrophages to induce Th1 development when Tcells were activated with dendritic cells. Furthermore, thisIL-12 mediated development of Th1 cells producing high levelsof IFN- was dependent on IFN-. 相似文献
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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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It has previously been described that V3 cells can proliferateextensively in vitro in the presence of different cytokines.Here, the role of cytokines in the maintenance of V3 cells inthe thymus has been determined. Culture of fetal thymocytesin cell suspension for 24 h showed that, whereas immature TCRlowHSAhighV3cells remained viable, all mature TCRhighHSAlowV cells died.These cells died by apoptosis since protein synthesis was requiredand flow cytometric analysis as well as DNA gel electrophoresisshowed that the DNA was degraded to oligonucleosomal bands.Addition of IL-2, IL-4 or IL-7 to suspension cultures of fetalthymocytes rescued V3 cells from dying. Addition of IL-1, IL-3,IL-5, IL-6, IL-9, TNE- or IFN- was without effect. Phenotypicanalysis showed that the -chain of the IL-2 receptor (IL-2R)was expressed by part of the immature V3 thymocytes, all matureV3 cells expressed the p-chain of the IL-2 receptor (IL-2RP).Addition of anti-IL-2R mAb to fetal thymic organ culture (FTOC)resulted in a moderate reduction of the cell number of matureV3 thymocytes. Addition of anti-IL-2Ra, anti-IL-4 or anti-IL-7mAb had no effect. The cell number of mature V3 cells was highlyreduced when both anti-IL-2Rp and anti-IL-7 mAb were added toFTOC. These results show that IL-2 and IL-7 are actively involvedin the maintenance of mature V3 cells in the thymus. This cytokinedependence of mature Vthymocytes may explain their selectivelocalization in skin epithelium. 相似文献
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Nanda Navreet K.; Sercarz Eli E.; Hsu Di-Hwel; Kronenberg Mitchell 《International immunology》1994,6(5):731-737
We report that the lymphokines (IFN-) and IL-10 are co-syntheslzedby previously described CD3+ TCRß+, minor antigen-specificsuppressor T cell clones. IFN- and IL-10 are known to (I) becharacteristically produced by different helper T cell types,Th1 and Th2 respectively, and (II) inhibit the function of thereciprocal subset of T cells: IFN- Inhibits the function ofTh2 and IL-10 that of Th1 cells. Although Th0 cells are alsoknown to synthesize cytoklnes of both the Th1- and Th2-typeT cells, the suppressor T cells described in this report aredifferent from Th0 cells in that they produce (I) neither IL-2nor IL-4 molecules and (II) stimulation via their CD3-TCR systemseems independent of both IL-2 and IL-4, the typical autocrinemolecules for T cell proliferation. The lymphokine profile ofthese suppressor T (TJ cell clones, as well as those of humanantigen-specific T. cells reported earlier, suggests that co-synthesisof some Th1-llke and some Th2-like cytoklnes may be a characteristicof antigen-specific T, cells as opposed to the type of reciprocalinhibition mediated through IFN- or IL-10, which is antigennon-specific. 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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Gieni Randall S.; Fang Yu; Trinchieri Giorgio; Umetsu Dale T.; DeKruyff Rosemarie H. 《International immunology》1996,8(10):1511-1520
The profile of cytokines produced by CD4 T cells is profoundlyinfluenced by the presence of IL-12. Here we demonstrate thatduring re-stimulation of antigen-specific immune responses invitro, antigen-primed lymph node cells from DBA/2 mice produced3- to 30-fold more IL-12 than did cells from BALB/c mice, whichare identical at the major histocompatibility locus. The straindifferences in IL-12 production were observed only in antigen-drivenresponses (and not in responses induced by bacterial products),and were dependent upon an interaction between CD4 T cells andlymph node adherent cells. In addition, differences in the quantityof IL-12 produced by DBA/2 and BALB/c antigen-presenting cells(APC) was not dependent on differential production of IFN- byT cells, since APC from DBA/2 mice still produced much greaterquantities of IL-12 than did BALB/c APC when each was culturedwith the same H-2d-restricted Th2 clones, in the complete absenceof IFN, or when each was cultured with primed (BALB/c x DBA/2)F1T cells. The level of IL-12 produced in the cultures criticallyaffected cytokine production in CD4 T cells, since neutralizationof endogenous IL-12 in DBA/2 cultures, which are predisposedtowards developing Th1 responses, reduced IFN- production andenhanced IL-4 synthesis to levels normally seen in BALB/c cultures,which are predisposed toward developing Th2 responses. We proposetherefore that differential production of antigen-driven IL-12is a mechanism by which the genetic background in DBA/2 andBALB/c mice can affect the pattern of cytokine synthesis byT cells during the development of adaptive immune responses. 相似文献
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Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection 总被引:13,自引:0,他引:13
Langhorne Jean; Gillard Sylvie; Simon Birgit; Slade Sally; Eichmann Klaus 《International immunology》1989,1(4):416-424
The functional heterogeneity of the CD4+ T cell response toPlasmodium chabaudi has been evaluated. Using a limiting dilutionassay system and a variety of assays to detect -interferon (IFN-),interleukln-2 (IL-2), IL-3, and T helper (Th) cells for malaria-specificantibody production, the precursor frequencies of P. chabaudl-reactiveT cells have been calculated. The patterns of lymphokines producedby individual microcultures of the limiting dilution assay generallysupported the Idea of two functionally distinct CD4+ subsets:one which produces IFN- and IL-2 (Th1) and one which Is an effectivehelper cell for antibody production (Th2) However, it couldnot be determined whether the overiapping functions observedin some cultures represented T cells which could produce allfactors or separate clones which were developing In the samewells. During the first 14 days of an erythrocytic Infectionof P. chabaudi the predominant T cell response was of the Th1-tupe.The frequency of these cells decreased after 14 days. By 3 weeksafter Infection the CD4+ T cell response was characterized byTh2 cells, as defined by their ability to act as helper cellsin the production of malaria-specific antibody. These data supportthe hypothesis that early clearance of P. chabaudi may be antibody-Independentbut that the final clearance mechanism coincides with the appearanceof helper cells and antibody. 相似文献
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In vivo and in vitro repertoire of CD3+CD4 CD8 thymocytes 总被引:3,自引:0,他引:3
CD4-CD8- thymocytes contain a cell subset which expresses thecomplete CD3-TCR complex (/ or /) of which the ontogeny andfiliation are unknown. One of the questions is whether thispopulation can be intrathymically selected, an obligatory stepfor the mature CD4+ and CD8+ cell differentiation pathway, orif the absence of CD4 and CD8 allows them to escape thymic selection.The repertoire of CD3 + CD4 - CD8 - (CD3 + DN) thymocytes wasanalyzed in different strains of mice with different combinationsof H-2 and Mls expression. The expression of Vß8.1in freshly isolated CD3+ DN cells is the highest in Mls-lb miceand the lowest in MIS-la and F1 mice, suggesting that selectionagainst this specificity can be achieved in vivo. By contrast,a low percentage of Vß6+ cells is found in all thestrains, with no correlation according to MIS expression. Invitro culture of DN thymocytes with IL-1 and IL-2 leads to theproliferation of CD3+ DN cells. In vitro culture amplifies thein vivo pattern of Vß8.1 expression, while Vß6+cells only expand in DN cells of 66 and 61002 Mls-lb mice withthe same genetic background. These results show: (i) CD3+ DNthymic cells can be intrathymically selected but the repertoireis different from that of mature T cells; (ii) Vß6and Vß8.1 selection do not follow the same pattern;(iii) this repertoire can be modified by In vitro culture, towarda more mature type; and (iv) comparison of DN cell repertoireof BALBlc, BALB.D2 (congenic for MLs), and other strains ofmice suggests a multigenic control for this selection, and aninvolvement of background genes. 相似文献