共查询到20条相似文献,搜索用时 15 毫秒
1.
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
2.
Horvath-Arcidiacono Judith A.; Mostowski Howard S.; Bloom Eda T. 《International immunology》1996,8(5):661-673
Because IL-12 restores allogeneic cytotoxic T lymphocyte (CTL)activity by T cells of aged mice in vitro, we initially assessedwhether IL-12 could overcome age-related deficits when givento aged mice in vivo. Growth of P815 (H-2d) was enhanced inaged compared with young BALB/c (H-2d) mice and tumor growthwas curtailed by IL-12 in both age groups. Unexpectedly, secondaryCTL stimulated ex vivo with P815 were reduced in IL-12-treatedmice compared with controls. Primary CTL generated ex vivo acrossMHC differences in IL-12-treated BALB/c and C57BL/6 young micewere reduced by 90–99%, were dose- and time-dependent,and were associated with reduced allo-stimulated NK-like activityand [3H]thymidine incorporation. IFN- was elevated in sera andin supernatants from allo-stimulated cultures from IL-12-treatedmice, while IL-4 was reduced in such supernatants, suggestingthat, despite reduced CTL, IL-12 was associated with increasedTh1- and reduced Th2-type cytokine production. IL-12 also inducedsplenomegaly, primarily due to increased numbers of cells lackingmarkers of mature T, B and NK cells, or macrophages, or polymorphonuclearleukocyte morphology. IFN- mutant mice exhibited reduced splenicenlargement in response to IL-12, suggesting that the splenomegalywas due, in part, to IFN- production. However, reduced CTL generationwas not due entirely to dilution of CTL precursor cells becausespleen cellularity and size increased 3-fold while CTL activitydecreased 10- to 100-fold, and CTL generation normalized toCD8+ T effector cells was still significantly reduced in IL-12-treatedmice. Interestingly, purified CD4+ and CD8+ T cells from IL-12-treatednormal mice exhibited greater proliferative and cytolytic activitiesrespectively compared with controls. Thus, effector T cellsin IL-12-treated mice were not impaired, but exhibited augmentedresponsiveness, suggesting that IL-12 induced complex interactionsamong spleen cell populations and that these effects, in part,are mediated by IFN-. 相似文献
3.
Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice 总被引:22,自引:0,他引:22
Powrie Fiona; Leach Michael W.; Mauze Smita; Caddie Linda Barcomb; Coffman Robert L. 《International immunology》1993,5(11):1461-1471
CD4+ T cells in the mouse can be subdivided into two fractionsbased on the level of expression of the CD45RB determinant.Previous studies have shown that these subsets are functionallydistinct. We have further characterized the properties of thesesubpopulations in vivo by injecting them into C. B-17 scid mice.The animals restored with the CD45RBhighCD4+ T cell populationdeveloped a lethal wasting disease with severe mononuclear cellinfiltrates into the colon and elevated levels of IFN- mRNA.In contrast, animals restored with the reciprocal CD45RBlowsubset or with unfractionated CD4+ T cells did not develop thewasting or colitis. Importantly, the co-transfer of the CD45RBlowpopulation with the CD45RBhigh population prevented the wastingdisease and colitis. These data indicate that important regulatoryinteractions occur between the CD45RBhigh and CD45RBlowCD4+T cell subsets and that disruption of this mechanism has fatalconsequences. 相似文献
4.
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
5.
6.
We have identified a small subset of CD3+, CD4+, CD8thymocytes that do not express Thy1 (CD90). This Thy1subset represents 13.7% of the total number of thymocytesin a naive mouse. CD4+Thy1 thymocytes express high levelsof CD3, intermediate to high levels of heat-stable antigen (HSA),and low levels of CD25, CD45RB, CD69, CD44 and CD62L. They producehigh titers of IL-4 and no IFN- upon stimulation in vitro, aresponse characteristic of Th2 cells. In the thymi of mice infectedneonatally with a high dose of the retrovirus Cas-Br-E MuLV,the frequency of CD4+Thy1 cells increased ~10-fold. High-dosevirus infection resulted in decreased HSA and increased CD44expression on CD4+Thy1 cells relative to cells from naivemice. CD4+Thy1 cells from high-dose infected mice alsosecreted IL-4 and not IFN- upon in vitro stimulation. We previouslyreported that infection of newborn mice with a high dose ofmurine retrovirus results in the induction of a non-protectiveanti-viral Th2 T cell response; CD4+Thy1 thymocytes witha Th2-like cytokine profile may play a role in determining thecytokine bias of this anti-viral response. 相似文献
7.
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
8.
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
9.
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
10.
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
11.
12.
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
13.
Nishimura Hiroyuki; Hattori Susumu; Ueda Genjiro; Abe Masaaki; Yang Kwangseok; Nozawa Shingo; Okamoto Hiroshi; Zhang Danqing; Tsurui Hiromichi; Hirose Sachiko; Shirai Toshikazu 《International immunology》1995,7(7):1115-1123
Using two mAb, one specific to the alternative exon 6-dependentepitope of CD45 molecules(JH6.2) and one a natural thymocytotoxicautoantibody (NTA) with an unknown reactive epitope (NTA260),we subdivided splenic CD4+ T cells from 2-month-old BALB/c miceinto five phenotypically distinct subsets. CD45RC+NTA260–(SI) cells were phenotypically analogous to CD4+ T cells predominatingin newborn mice and produced a significant amount of IL-2, butnot so IL-4, IL-10 or IFN- when stimulated with immobilizedanti-CD3 mAb in vitro. They appeared to consist mainly of naiveThP cells. The CD45RC+;NTA260+ (S II) subset also produced IL-2,but not other cytokines; however, the IL-2 levels produced weremuch higher than seen with the S I subset, thereby suggestingthe predominance of further maturated ThP cells. The D45RC–NTA260+(S III) subset mainly produced IL-4, IL-10, IFN- and less IL-2,and contained memory cells that helped the secondary antibodyresponse to a recall antigen, and hence contained Th2 and probablya mixture of Th0 and Th1 cells. The CD45RC–NTA260–(S IV) subset was a poor responder to the immobilized anti-CD3mAb. The CD45RCbrightNTA260dull(S V) subset consisted of a smallnumber of cells that were phenotypically analogous to activatedCD4+ T cells. While an age-associated decrease in the proportionof S I and less markedly in S II and in turn increase in S IIIsubsets of CD4+ T cells occurred in normal BALB/c mice, autoimmunedisease-prone (NZBxNZW)F1 mice showed a marked age-associateddecrease in the proportion of not only S I, II but also IIIsubsets. As aged (NZBxNZW)F1 mice carry CD4+ T helper cellsfor IgG anti-DNA antibody production, such age-associated polarizationto the S IV subset appears to be critical in the pathogeneslsof autoimmune disease in these mice. 相似文献
14.
Vicari Alain P.; Herbelin Andre; Leite-de-Moraeas Maria do Carmo; Freeden-Jeffry Ursula Von; Murray Richard; Zlotnik Albert 《International immunology》1996,8(11):1759-1766
Particular subsets of T cells expressing the NK1.1 antigen havebeen proposed to play an immune regulatory role by their fastand strong production of cytokines, in particular IL-4. We soughtto determine factors driving the functional differentiationof NK1.1+ T cells. Since NK1.1+ T cells are exquisitely sensitiveto IL-7 stimulation, we analyzed the development, selectionand IL-4 production of NK1.1+ T cells in IL-7 deficient mice(IL-7–/–mice). Besides a sharp reduction of allT cell subsets, NK1.1+ T cells develop at normal relative frequenciesin IL-7–/–;mice. They also undergo a normal selectionprocess, as revealed by the biased Vß TCR repertoireidentical to the one in IL-7+/+ mice. However, NK1.1+ T cellsfrom IL-7+/+ mice were found to be impaired in IL-4 and IFN-production in in vitro and in vivo models. In addition, IL-7was able to restore IL-4 production by NK1.1+ thymocytes fromIL-7–/– mice. Finally, IL-7 but not IL-4 was ableto maintain and increase IL-4 production by NK1.1+ thymocytesfrom normal mice. These data suggest that the functional maturationof NK1.1+ T cells requires a cytokine-driven differentiationprocess, in which IL-7 plays a major role. 相似文献
15.
Morris Lynn; Aebischer Toni; Handman Emanuela; Kelso Anne 《International immunology》1993,5(7):761-767
BALB/c mice are highly susceptible to infection with the protozoanparasite Leishmania major and develop a chronic fatal disease.They can, however, be manipulated to resist disease and thishas been shown to correlate with increased expression of IFN–mRNA and the absence of IL-4 mRNA in the draining lymph nodesand spleens of these animals. Here we show that anti-IL-4 oranti-CD4 treatment of BALB/c mice resulted in a reduction inthe size of the lesion and in the number of parasites in thedraining lymph nodes compared with untreated mice. The precursorfrequency of CD4+ T cells proliferating in response to Leishmaniaantigens in vitro in the treated animals was not significantlydifferent from untreated animals. Analysis of the lymphokinessecreted by the clonal progeny of these cells showed that theprecursor frequency of IL-4 secreting clones was at least 10-foldlower in animals treated with either mAb. However, there wasno reciprocal increase in the precursor frequencies of IFN–secreting clones. Comparisons of the total number of precursorsof specific CD4+ cells secreting IFN– showed that anti-CD4-treatedanimals, which are resistant to disease, had considerably fewerfor the first 6 weeks than untreated mice with chronic disease.Protection of BALB/c mice was therefore associated with a reductionin the numbers of precursors of cells secreting IL-4 withouta concomitant increase in the number of precursors of IFN–secreting cells. 相似文献
16.
Rojo JM Pini E Ojeda G Bello R Dong C Flavell RA Dianzani U Portolés P 《International immunology》2008,20(4):577-589
The inducible co-stimulator (ICOS, CD278) is essential to theefficient development of normal and pathological immune reactions.Since ICOS-deficient mice have enhanced susceptibility to experimentalallergic encephalomyelitis (EAE), we have functionally analyzeda CD4+ICOS+ population comprising 6–15% of all CD4+ Tcells in secondary lymphoid organs of unmanipulated wild-typemice and checked for their ability to suppress EAE. In C57BL/6mice, CD4+ICOS+ cells were a major source of cytokines includingIFN-, IL-2, IL-4, IL-10 or IL-17A. Upon activation, these cellsshowed preferentially enhanced production of IL-4 or IL-10 butinhibited IFN- production. In contrast, CD4+ICOS– cellsmainly produced IFN-. Interestingly, CD4+ICOS+ cells partiallysuppressed the proliferation of CD4+ICOS– or CD4+CD25–lymphocytes in vitro by an IL-10-dependent mechanism.Furthermore, CD4+ICOS+ activated and expanded under appropriateconditions yielded a population enriched in cells producingIL-10 and Th2 cytokines that also suppressed the proliferationof CD4+CD25– lymphocytes. CD4+ICOS+ cells, before or afterexpansion in vitro, reduced the severity of EAE when transferredto ICOS-deficient mice. In the same EAE model, lymph node cellsfrom ICOS-deficient mice receiving ICOS+ cells showed reducedIL-17A production and enhanced IL-10 secretion upon antigenactivation in vitro. Thus, naturally occurring CD4+ICOS+ cells,expanded or not in vitro, are functionally relevant cells ableof protecting ICOS-deficient mice from severe EAE. 相似文献
17.
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
18.
Anergy in vivo: down-regulation of antigen-specific CD4+ Th1 but not Th2 cytokine responses 总被引:1,自引:0,他引:1
Karpus William J.; Peterson Jeffrey D.; Miller Stephen D. 《International immunology》1994,6(5):721-730
Efficient immunologic tolerance, defined as antlgen-speclflcunresponslveness, can be peripherally induced by the l.v. Injectionof syngenelc splenocytes coupled with antigen using ethylenecarbodilmlde (ECDI). We have previously reported that unresponslvenessinduced via l.v. Injection of syngenelc splenocytes coupledwith intact, UV-lnactlvated Theiler's murine encephalomyelitisvirus (TMEV-SP) resulted in split tolerance. Bothvtrus-speclflc delayed-type hypersensltlvlty and lgG2a levelswere inhibited, whereas lgG1 levels were increased when comparedwith sham tolerized controls. In the present report we demonstratethat tolerance induced by l.v. Injection of TMEV-coupled splenocytesresulted in antigen-specific inhibition of T cell proliferation,as well as IL-2 and IFN- production in response to both wholeTMEV and the immunodomlnant viral epitope. Additionally, toleranceinduction resulted in abrogation of Th1 -derived [IL-2, IFN-and LT/tumor necrosis factor-ß (TNF-ß)]cytokine mRNA expression in response to In vitro stimulationwith UV-inactlvated TMEV as determined by reverse transcrlptasepolymerase chain reaction. In contrast, expression of Th2-derived(IL-4, IL-6 and IL-10) cytokine mRNA was not affected in tolerizedmice. Tolerance functioned directly at the level of CD4+ Th1cells at both the induction and effector limbs as depletionof CD8+ T cells both prior to in vivo tolerizatlon or in vitroculture had no effect on inhibition of Th1-specific responses.The mechanism of In vivo tolerance induction appeared to beanergy of CD4+ Th1 cells since IL-2, IFN- and LT/TNF-ßmRNA expression as well as virus-specific prollferatlve responsescould be restored by addition of rlL-2 to In vitro culturesof tolerant, CD4+ Th1 populations. These results suggest thatin vivo split tolerance Induced by l.v. Injectionof ECDI-flxed, antigen-coupled splenocytes involves anergy ofTMEV-speclflc, CD4+ Th1 lymphocytes and concomitant primingof Th2 cells. The induction of antlgen-speclflc, in vivo anergyhas important implications in the design of therapeutic strategiesfor immunopathologic diseases mediated by Th1 lymphocytes, especiallyT cell-mediated autoimmune disorders. 相似文献
19.
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
20.
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