共查询到20条相似文献,搜索用时 15 毫秒
1.
Tolerance and contact sensitivity to DNFB in mice. VI. Inhibition of afferent sensitivity by suppressor T cells in adoptive tolerance. 总被引:5,自引:0,他引:5
J W Moorhead 《Journal of immunology (Baltimore, Md. : 1950)》1976,117(3):802-806
Tolerance in contact sensitivity to DNFB can be adoptively transferred to normal mice with lymph node cells from tolerant donors. This tolerance is antigen specific and is mediated by T cells, i.e., "suppressor" T cells. Experiments were carried out to investigate the mechanism(s) by which the suppressor T cells induce tolerance to DNFB contact sensitivity. The suppressor cells were effective only if they were present during the early stages of the afferent limb of sensitization. As measured by DNA synthesis, cell proliferation in the draining lymph nodes of recipients of suppressor cells was found to be significantly less than in control animals indicating that the suppressor cells acted, at least in part, by limiting or inhibiting DNFB-induced cell proliferation. This inhibition was shown to be antigen specific since the DNFB suppressor cells did not inhibit cell proliferation induced by oxazolone, an unrelated contact sensitizer. The ability to DNFB tolerant cells to block afferent sensitization pathways differs from the mechanism of tolerance to picryl chloride, reported by others, where efferent pathways are blocked. 相似文献
2.
We investigated the mechanism(s) by which MHC-restricted suppressor T cells (Ts) induced by i.v. injection of allogeneic DNP-modified lymphoid cells (alloinduced Ts) suppress the DNFB contact sensitivity response. It was shown that alloinduced Ts acted only during the early phases (afferent limb) of sensitization. They were incapable of suppressing previously sensitized recipients or of inhibiting the expression of DNFB-immune LN cells when co-transferred into normal recipients. The target of alloinduced Ts seems to be cell proliferation, i.e., inhibition of antigen-induced cell proliferation (DNA synthesis) in Ts recipient mice. The failure of recipients of alloinduced Ts to generate DNFB-immune LN cells capable of transferring contact sensitivity to normal recipients also suggests that these Ts act by preventing the development of an expanded clone of mature immune T cells. The suppressive effects of alloinduced Ts also were inhibited by prior in vitro treatment with anti-TNP serum. The data are discussed in terms of current models of suppression, and are compared to mechanisms of suppression in other contact sensitivity models. 相似文献
3.
Contact sensitivity responses to dinitrofluorobenzene (DNFB) or oxazolone were enhanced by amphotericin B (AmB) administration. This adjuvant effect of AmB was documented in mice by ear thickness measurements, ear histology, and the 5-iodo-2'-deoxyuridine-125I ear assay. The optimum immunopotentiating effect of AmB required its simultaneous administration at the time of skin sensitization. AmB-induced adjuvant effects were also observed in adoptive transfer experiments in which syngeneic recipients of lymph node cells from animals sensitized with DNFB plus AmB gave stronger contact sensitivity responses than recipients of cells from mice sensitized with DNFB alone. AmB also interfered with tolerance induction by i.v. dinitrobenzene sulfonic acid, suggesting that its adjuvant effects involve inhibition of suppressor cells or their precursors. 相似文献
4.
Regulation of contact sensitivity to DNFB in the mouse: effects of adult thymectomy and thymic factor. 总被引:5,自引:0,他引:5
D Erard J Charreire M T Auffredou P Galanaud J F Bach 《Journal of immunology (Baltimore, Md. : 1950)》1979,123(4):1573-1576
The contact sensitivity response to DNFB is decreased after adult thymectomy (ATX). This response decreases to 50% of the control response of normal age-matched mice as soon as 3 weeks after ATX and is not further depressed 9 to 16 weeks after ATX. These results suggest that two T cell subsets of different lifespan are involved in the anti-DNFB response. A circulating thymic factor (FTS) is able to restore the contact sensitivity response to DNFB when injected 3 to 9 weeks after ATX but not 16 weeks later. By contrast, FTS has a depressive effect on the contact sensitivity response to DNFB of normal mice through a cyclophosphamide-sensitive T cell subset. These results suggest that FTS regulates DNFB contact sensitivity by acting on a cyclophosphamide-sensitive T cell subset, still present 9 weeks after ATX but absent after 16 weeks. Thus although the T cell defect, causing a depression of the contact sensitivity reaction to DNFB is quantitatively similar 3 and 16 weeks after ATX, its nature is probably different. 相似文献
5.
We investigated the down-regulation of contact sensitivity (desensitization) in mice sensitized to DNFB. Mice were sensitized with DNFB, desensitized with antigen 2 wk later, and resensitized 2 wk after desensitization. Large doses of antigen (DNFB or DNBSO3) produced about 50% inhibition of the anamnestic response as measured by ear swelling after challenge with DNFB. Desensitization was antigen specific and long lasting. Lymph node cells from desensitized mice showed diminished antigen-induced proliferation in vitro. Although the anamnestic response can be inhibited by afferent- or efferent-acting suppressor cells, such suppressor cells were not demonstrated in desensitized animals. The most likely explanation is that antigen desensitizes by inactivating effector cells for contact sensitivity, although suppressor mechanisms have not been completely excluded. 相似文献
6.
Gorbachev AV Heeger PS Fairchild RL 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(4):2323-2332
The primary effector cells of contact hypersensitivity (CHS) responses to dintrofluorobenzene (DNFB) are IFN-gamma-producing CD8(+) T cells, whereas CD4(+) T cells regulate the magnitude and duration of the response. The requirement for CD40-CD154 engagement during CD8(+) and CD4(+) T cell priming by hapten-presenting Langerhans cells (hpLC) is undefined and was tested in the current study. Similar CHS responses to DNFB were elicited in wild-type and CD154(-/-) animals. DNFB sensitization of CD154(-/-) mice primed IFN-gamma-producing CD8(+) T cells and IL-4-producing CD4(+) T cells. However, anti-CD154 mAb MR1 given during hapten sensitization inhibited hapten-specific CD8(+), but not CD4(+), T cell development and the CHS response to challenge. F(ab')(2) of MR1 failed to inhibit CD8(+) T cell development and the CHS response suggesting that the mechanism of inhibition is distinct from that of CD40-CD154 blockade. Furthermore, anti-CD154 mAb did not inhibit CD8(+) T cell development and CHS responses in mice depleted of CD4(+) T cells or in CD4(-/-) mice. During in vitro proliferation assays, hpLC from mice treated with anti-CD154 mAb during DNFB sensitization were less stimulatory for hapten-primed T cells than hpLC from either control mice or mice depleted of CD4(+) T cells before anti-CD154 mAb administration. These results demonstrate that development of IFN-gamma-producing CD8(+) T cells and the CHS response are not dependent on CD40-CD154 interactions. This study proposes a novel mechanism of anti-CD154 mAb-mediated inhibition of CD8(+) T cell development where anti-CD154 mAb acts indirectly through CD4(+) T cells to impair the ability of hpLC to prime CD8(+) T cells. 相似文献
7.
Application of 2,4-dinitrofluorobenzene (DNFB) to BALB/c mouse skin depleted of epidermal Langerhans cells (LC) by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) activated cells which suppress both contact sensitivity and antibody production when transferred into naive host mice. Tolerance was induced by a concentration of DNFB optimal for inducing contact sensitivity in solvent-treated control mice. The cellular and humoral responses of hosts to a second antigen, 2,4,6-trinitrochlorobenzene (TNCB), were unaffected by these suppressor cells, demonstrating specificity for DNFB. Suppressor cells for cellular and humoral immunity could still be demonstrated 6 months following activation, by which time some mice had died, presumably of old age. The dose responses to sensitizer for generation of cells which suppressed contact sensitivity and antibody production differed, indicating that separate populations of suppressor cells probably inhibit these responses. Hence, during cutaneous chemical carcinogenesis, depletion of LC may allow activation of specific long-lived suppressor cells capable of inhibiting cellular or humoral antitumor immune responses. 相似文献
8.
Robertson SJ Ammann CG Messer RJ Carmody AB Myers L Dittmer U Nair S Gerlach N Evans LH Cafruny WA Hasenkrug KJ 《Journal of virology》2008,82(1):408-418
Friend virus (FV) and lactate dehydrogenase-elevating virus (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found that numerous mouse-passaged FV isolates also contained LDV and that coinfection with LDV delayed FV-specific CD8+ T-cell responses during acute infection. While LDV did not alter the type of acute pathology induced by FV, which was severe splenomegaly caused by erythroproliferation, the immunosuppression mediated by LDV increased both the severity and the duration of FV infection. Compared to mice infected with FV alone, those coinfected with both FV and LDV had delayed CD8+ T-cell responses, as measured by FV-specific tetramers. This delayed response accounted for the prolonged and exacerbated acute phase of FV infection. Suppression of FV-specific CD8+ T-cell responses occurred not only in mice infected concomitantly with LDV but also in mice chronically infected with LDV 8 weeks prior to infection with FV. The LDV-induced suppression was not mediated by T regulatory cells, and no inhibition of the CD4+ T-cell or antibody responses was observed. Considering that most human adults are carriers of chronically infectious viruses at the time of new virus insults and that coinfections with viruses such as human immunodeficiency virus and hepatitis C virus are currently epidemic, it is of great interest to determine how infection with one virus may impact host responses to a second infection. Coinfection of mice with LDV and FV provides a well-defined, natural host model for such studies. 相似文献
9.
Oral administration of hapten inhibits in vivo induction of specific cytotoxic CD8+ T cells mediating tissue inflammation: a role for regulatory CD4+ T cells 总被引:10,自引:0,他引:10
Desvignes C Etchart N Kehren J Akiba I Nicolas JF Kaiserlian D 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(5):2515-2522
We investigated whether oral tolerance could block the development of an inflammatory response mediated by CD8+ T cells, using a mouse model of oral tolerance of contact sensitivity (CS) to the hapten 2, 4-dinitrofluorobenzene (DNFB). In this system, the skin inflammatory response is initiated by hapten-specific class I-restricted cytotoxic CD8+ T (CTL) cells, independently of CD4 help. Oral delivery of DNFB before skin sensitization blocked the CS response by impairing the development of DNFB-specific CD8+ effector T cells in secondary lymphoid organs. This was shown by complete inhibition of DNFB-specific CTL and proliferative responses of CD8+ T cells, lack of specific IFN-gamma-producing CD8+ T cells, and inability of CD8+ T cells to transfer CS in RAG20/0 mice. RT-PCR and immunohistochemical analysis confirmed that recruitment of CD8+ effectors of CS in the skin at the site of hapten challenge was impaired in orally tolerized mice. Sequential anti-CD4 Ab treatment showed that only depletion of CD4+ T cells during the afferent phase of CS abrogated oral tolerance induction by restoring high numbers of specific CD8+ effectors in lymphoid organs, whereas CD4 depletion during the efferent phase of CS did not affect oral tolerance. These data demonstrate that a single intragastric administration of hapten can block in vivo induction of DNFB-specific CD8+ CTL responsible for tissue inflammation and that a subset of regulatory CD4+ T cells mediate oral tolerance by inhibiting expansion of specific CD8+ effectors in lymph nodes. 相似文献
10.
The immediate effects and mechanisms of desensitization of contact sensitivity to 2,4-dinitro-1-fluorobenzene (DNFB) were investigated. Mice were sensitized with DNFB, desensitized with antigen 2 weeks later, and challenged 1 day after desensitization. Significant inhibition (approximately 50%) of contact sensitivity was observed after iv injections of large doses of dinitrobenzene sulfonic acid (DNBS) or dinitropenol (DNP)-labeled spleen cells. Haptenated red blood cells (RBC) did not induce any significant immediate desensitization but produced significant inhibition of an anamnestic response 2 weeks later. The immediate desensitization induced by DNBS was antigen nonspecific. Although the contact sensitivity response itself could be inhibited by afferent- or efferent-acting suppressor cells, such cells were not demonstrated in desensitized animals. DNBS appears to desensitize by inactivating effector cells for contact sensitivity, although it appears that suppressor mechanisms could be activated by other physiochemical forms of the desensitizing antigen. 相似文献
11.
W R Thomas M C Watkins G L Asherson 《Journal of immunology (Baltimore, Md. : 1950)》1979,122(6):2300-2303
Previous reports have shown that picryl sulfonic acid (PSA) induces suppressor T cells that inhibit the effector phase of contact sensitivity, whereeas its DNP counterpart, dinitrobenzenesulfonate (DNBS) induces cells that inhibit the afferent phase of sensitization. Accordingly, cells from mice injected with DNBS, but not PSA, could be shown to inhibit the DNA synthesis in the lymph nodes that occurs during sensitization. It is now shown that PSA does induce T cells that suppress DNA synthesis but this can only be detected with enriched T cells or by using a regimen of PSA injection different frm previously used to induce suppressor cells for the effector phase. The T cells did not affect responses to oxazolone or dinitrofluorobenzene (DNFB) and were distinguishable from suppressors of the efferent phase in that they could be produced in adult thymectomized but not cyclophosphamide-treated mice. T cells from mice injected with DNBS that inhibited DNA synthesis to DNFB had the same properties. 相似文献
12.
The effect of increasing age on various tests of cell-mediated immunity was investigated in BALB/c mice both in vitro and in vivo with four different assay systems. The following results were obtained. 1) In contact sensitivity to DNFB, old mice (age 60 to 80 weeks) showed no differences in sensitization when compared to young adult mice (age 8 to 12 weeks). (In contrast, old NZB/W mice showed impaired contact sensitization when compared with young NZB/W MICE.)2) Unlike the reaction in contact sensitivity, cells from old BALB/c mice were defective in eliciting a graft-vs-host reaction. This was true also when a partially purified population of T cells was transferred. 3) In the mixed lymphocyte reaction, cells from old mice were as efficient or better than cells from young adult BALB/c mice in responding to or stimulating allogeneic cells. 4) Responses to PHA and Con A (Both T cell mitogens) were greatly reduced when old cells were cultured as compared with cells from young adult mice. Thus, we have found that within the same batch of mice, increasing age was associated with increased capabilities in some measures of cell-mediated immunologic function and decreased capabilities in other measures of the same. 相似文献
13.
Comprehensive early and lasting loss of memory CD8 T cells and functional memory during acute and persistent viral infections 总被引:5,自引:0,他引:5
Viral infections have been shown to induce lymphopenias that lower memory CD8 T cell frequencies, and they also have been shown to cause a permanent loss of memory cells specific to previously encountered pathogens. In this study, the patterns and significance of virus-induced memory CD8 T cell depletion were examined in mice immune to heterologous (Pichinde, vesicular stomatitis, vaccinia) viruses and subsequently challenged with acute or persistent lymphocytic choriomeningitis virus infections. Memory CD8 T cell loss was comprehensive and occurred in both lymphoid and peripheral tissues of the immune host. The impact of the loss of memory T cells was reflected by in vivo cytotoxicity assays, which showed decreased clearance of epitope-expressing targets. Memory CD8 T cell loss occurred very early (day 2) after infection, and was thereafter sustained, consistent more with an active deletion model than with a competition model. Cross-reactive T cells, in contrast, increased in number, but memory cells were reduced whether or not there was competition from cross-reactive T cells. Memory T cell loss was more profound during persistent infection than after acute infection. Adoptive transfer studies showed that, unlike the resolved acute infection, in which the reduced memory frequencies became stable, memory T cell loss was a continuously ongoing process during persistent infection. This study therefore links an early virus-induced lymphopenia to a subsequent long-term loss of CD8 T cell memory and offers a new mechanism for immune deficiency during persistent viral infections. 相似文献
14.
Phenotypic and functional characterization of ultraviolet radiation-induced regulatory T cells 总被引:1,自引:0,他引:1
Maeda A Beissert S Schwarz T Schwarz A 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(5):3065-3071
Sensitization through UV-exposed skin induces regulatory T cells (Treg). In contrast to the classical CD4+CD25+ Treg that act contact dependent, UV-induced Treg (UV-Treg) suppress via IL-10, indicating a distinct subtype that requires further characterization. Depletion studies revealed that UV-Treg express the glucocorticoid-induced TNF family-related receptor (GITR) and the surface molecule neuropilin-1. The injection of T cells from UV-tolerized mice after depletion of UV-Treg into naive recipients enabled a contact hypersensitivity response, indicating that tolerization also induces T effector cells. Adoptive transfer experiments using IL-10-deficient mice indicated that the IL-10 required for suppression is derived from UV-Treg and not from host-derived cells. Activation of UV-Treg is Ag specific, however, once activated suppression is nonspecific (bystander suppression). Hence, speculations exist about the therapeutic potential of Treg generated in response to Ag that are not necessarily the precise Ag driving the pathogenic process. Thus, we studied the consequences of multiple injections of 2,4-dintrofluorobenzene (DNFB)-specific Treg into ears of naive mice followed by multiple DNFB challenges. DNFB-specific Treg were injected once weekly into the left ears of naive mice and DNFB challenge was performed always 24 h later. After three injections, a challenging dose of DNFB was applied on the right ear. This resulted in pronounced ear swelling, indicating that the subsequent boosting of DNFB-specific Treg had caused sensitization of the naive mice against DNFB. These data demonstrate that UV-Treg express GITR and neuropilin-1 and act via bystander suppression. However, constant boosting of Treg with Ag doses in the challenging range results in final sensitization that might limit their therapeutic potential. 相似文献
15.
Immunomodulating activities of staphylococcal enterotoxins. I. Effects on in vivo antibody responses and contact sensitivity reaction 总被引:2,自引:0,他引:2
K Kawaguchi-Nagata H Okamura K Shoji H Kanagawa M Semma K Shinagawa 《Microbiology and immunology》1985,29(3):183-193
The immunomodulating effects of staphylococcal enterotoxins on in vivo immune responses in C57BL/6 mice were examined. Of the five serological types A (SEA), B, C, D, and E (SEE), only SEA and SEE markedly suppressed the antibody response to sheep red blood cells (SRBC) when injected 1 day before or on the day of immunization with SRBC. Further study of SEA revealed that it did not affect the antibody response to a thymus-independent antigen, salmonella flagella, but did affect the T-cell-mediated immune response. Contact sensitivity to dinitrofluorobenzene (DNFB) was suppressed when SEA was injected before sensitization or before challenge with DNFB, indicating that SEA affected both the afferent and efferent phases of DNFB contact sensitivity. As the suppression of DNFB contact sensitivity could be transferred by anti-Thy-1.2 antibody-sensitive spleen cells of SEA injected donors into normal or DNFB-sensitized recipients, the suppression was thought to be an active one. However, SEA could augment the DNFB contact sensitivity when injected on the third day after sensitization with DNFB. These results indicate that the immunomodulating effects of SEA can be mediated by the T-cell function. 相似文献
16.
Klaus D. Elgert 《Cellular immunology》1980,49(2):395-401
Fibrosarcoma-bearing BALB/c mice were assessed for 2,4-dinitroflurobenzene (DNFB)-induced contact sensitivity by a quantitative radioisotopic ear assay. Measurement of contact sensitivity was based on the localization of intraperitoneally injected iodinated-human serum albumin ([125I]HSA) in the challenged ear. Normal and tumor-bearing mice (TBM) had optimal localization 4 days after sensitization, as determined by challenging with DNFB ear application and measuring increased vascular permeability of the challenged ear over the unchallenged ear. However, at all times TBM responsiveness to challenge was significantly lower than that of the normal population. Kinetic experiments indicated that the most dramatic decrease in TBM primary and secondary cell-mediated immune response to the contact sensitizing agent occurred 15 to 19 days post tumor transplant, flattening out to a consistently low level during the fourth and fifth week of tumor growth. Results from these in vivo experiments strongly corroborate our previous in vitro inhibition data from tumor-induced nonspecific suppressor cells. 相似文献
17.
Lactate dehydrogenase-elevating virus replication persists in liver, spleen, lymph node, and testis tissues and results in accumulation of viral RNA in germinal centers, concomitant with polyclonal activation of B cells. 总被引:6,自引:4,他引:2
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lactate dehydrogenase-elevating virus (LDV) replicates primarily and most likely solely in a subpopulation of macrophages in extraneuronal tissues. Infection of mice, regardless of age, with LDV leads to the rapid cytocidal replication of the virus in these cells, resulting in the release of large amounts of LDV into the circulation. The infection then progresses into life-long, asymptomatic, low-level viremic persistence, which is maintained by LDV replication in newly generated LDV-permissive cells which escapes all antiviral immune responses. In situ hybridization studies of tissue sections of adult FVB mice revealed that by 1 day postinfection (p.i.), LDV-infected cells were present in practically all tissues but were present in the highest numbers in the lymph nodes, spleen, and skin. In the central nervous system, LDV-infected cells were restricted to the leptomeninges. Most of the infected cells had disappeared at 3 days p.i., consistent with the cytocidal nature of the LDV infection, except for small numbers in lymph node, spleen, liver, and testis tissues. These tissues harbored infected cells until at least 90 days p.i. The results suggest that the generation of LDV-permissive cells during the persistent phase is restricted to these tissues. The continued presence of LDV-infected cells in testis tissue suggests the possibility of LDV release in semen and sexual transmission. Most striking was the accumulation of large amounts of LDV RNA in newly generated germinal centers of lymph nodes and the spleen. The LDV RNA was not associated with infected cells but was probably associated with virions or debris of infected, lysed cells. The appearance of LDV RNA in germinal centers in these mice coincided in time with the polyclonal activation of B cells, which leads to the accumulation of polyclonal immunoglobulin G2a and low-molecular-weight immune complexes in the circulation. 相似文献
18.
Akbar H Germon S Berthon P Dimier-Poisson I Moiré N 《Memórias do Instituto Oswaldo Cruz》2012,107(2):155-162
The interleukin (IL)-2R alpha chain (CD25) is expressed on regulatory T cells (Treg), which constitute more than 85% of the CD25+ T cell population in a na?ve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody. 相似文献
19.
Pseudotype virions formed between mouse hepatitis virus and lactate dehydrogenase-elevating virus (LDV) mediate LDV replication in cells resistant to infection by LDV virions.
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Infection of cultures of peritoneal macrophages with both lactate dehydrogenase-elevating virus (LDV) and mouse hepatitis virus (MHV) resulted in the formation of pseudotype virions containing LDV RNA which productively infected cells that are resistant to infection by intact LDV virions but not to infection by MHV. These cells were mouse L-2 and 3T3-17Cl-1 cells as well as residual peritoneal macrophages from persistently LDV-infected mice. Productive LDV infection of these cells via pseudotype virions was inhibited by antibodies to the MHV spike protein or to the MHV receptor, indicating that LDV RNA entered the cells via particles containing the MHV envelope. Simultaneous exposure of L-2 cells to both LDV and MHV resulted in infection by MHV but not by LDV. The results indicate that an internal block to LDV replication is not the cause of the LDV nonpermissiveness of many cell types, including the majority of the macrophages in an adult mouse. Instead, LDV permissiveness is restricted to a subpopulation of mouse macrophages because only these cells possess a surface component that acts as an LDV receptor. 相似文献
20.
IL-12-independent IFN-gamma production by T cells in experimental Chagas' disease is mediated by IL-18. 总被引:8,自引:0,他引:8
U Müller G K?hler H Mossmann G A Schaub G Alber J P Di Santo F Brombacher C H?lscher 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(6):3346-3353
IL-12p35-deficient (IL-12p35(-/-)) mice were highly susceptible to Trypanosoma cruzi infection and succumbed during acute infection, demonstrating the crucial importance of endogenous IL-12 in resistance to experimental Chagas' disease. Delayed immune responses were observed in mutant mice, although comparable IFN-gamma and TNF-alpha blood levels as in wild-type mice were detected 2 wk postinfection. In vivo and in vitro analysis demonstrated that T cells, but not NK cells, were recruited to infected organs. Analysis of mice double deficient in the recombinase-activating gene 2 (RAG2) and IL-12p35, as well as studies involving T cell depletion, identified CD4(+) T cells as the cellular source for IL-12-independent IFN-gamma production. IL-18 was induced in IL-12p35(-/-) mice and was responsible for IFN-gamma production, as demonstrated by in vivo IL-18 neutralization studies. In conclusion, evidence is presented for an IL-12-independent IFN-gamma production in experimental Chagas' disease that is T cell and IL-18 dependent. 相似文献