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At least 19 recordsLinked to original sources
PubMed1999

Cytokines that regulate autoimmune responses.

Autoimmune responses are controlled by complex regulatory circuits. Previous work has revealed that factors controlling autoimmunity can act both as potentiating and inhibitory agents, depending upon the site and timing of exposure. Recent advances in this complex field have at least partially uncovered the mechanism whereby these regulatory molecules participate in autoimmune processes. IL-12 production in the absence of infection may predispose to autoimmunity. IL-4 and transforming growth factor beta may suppress autoreactive T cells. Proinflammatory cytokines may ameliorate autoimmunity, dependent on the timing and level of production. In many cases, cytokines may act via antigen-presenting cells.

Animals↗
PubMed2000

Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis.

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.

Animals↗
PubMed2005

High level of cross-reactivity in influenza virus hemagglutinin-specific CD4+ T-cell response: implications for the initiation of autoimmune response in multiple sclerosis.

Viral infections play a role in shaping and maintaining the peripheral T-cell repertoire, as well as in the initiation of autoimmune response via mechanisms of molecular mimicry. In this study, we addressed the flexibility of T-cell receptor (TCR) recognition and the degree of structural and sequence homology required for cross-reactive immune response in the induction of autoimmune response. We studied the extent of cross-reactivity of a CD4+T-cell clone (TCC) specific for the immunodominant influenza virus hemagglutinin (Flu-HA) peptide derived from a patient with multiple sclerosis (MS) using positional scanning synthetic peptide combinatorial libraries (PS-SCL). We documented cross-reactivity against 14 Flu-HA variants, 11 viral, 15 human, and 3 myelin-derived peptides. Moreover, we identified six naturally occurring peptides with higher stimulatory potency than the native ligand, implicating high potential for cross-reactivity even for a virus-specific memory TCC. Our study demonstrates that flexibility of TCR recognition is present even in a clone with a high degree of TCR specificity for an infectious agent. The results have implications for vaccine design and for antigen-specific treatment strategies for autoimmune diseases.

CD4-Positive T-Lymphocytes↗
PubMed1998

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response.

Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T4), triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T4, but more T3, than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T4, but equal amounts of T3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-alpha were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes in these infiltrations. At the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a small hyperplastic goitre. At that time there is also in vitro evidence for a shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth abnormalities have been described in another animal model of thyroid autoimmune disease, the obese strain chicken.

Animals↗
PubMed1995

[Murine "sympathetic orchitis" induced by unilateral testicular injury and autoimmune response].

BACKGROUND: Experimental autoimmune orchitis (EAO) has been studied as an animal model for human male immunological infertility. Most EAO models have been induced by immunization with testis antigens in artificial adjuvants. In this paper, we report a more clinical EAO model. METHODS: Ten to 20 needle punctures were made to the unilateral testis of mice and it was crushed by a needle-holder. RESULTS: Contralateral EAO (so-called "sympathetic orchitis") was gradually induced starting on Day 28. Delayed type hypersensitivity (DTH), one of the cell-mediated immunities, to autologous testicular cells (TC) as well as anti-TC antibodies, humoral immunity, were both detected in those mice. Repeated crush(es) of the ipsilateral testis two weeks later (and four weeks later) as a booster did not enhance the contralateral lesion or autoimmune responses. CONCLUSION: Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility.

Animals↗
PubMed1990

IgE dependent autoimmune response. Effect of Trypanosoma cruzi infection.

The autoimmune response to mouse accessory glands (MAG) was investigated in male BALB/c mice immunized with different doses of chemically modified mouse accessory glands (MMAG) and complete Freund's adjuvant (CFA). This autoimmune response was studied at several time intervals using the skin test with MAG. It was found that 5 mg of MMAG induced on the day 15 an autoimmune response detected by specific skin test at 20 min., 3 h and 24 h. The results of the immediate type hypersensitivity (ITH) were higher than those with the other skin tests. In order to study the type of immunoglobulin involved, the ITH was also analyzed by passive cutaneous anaphylaxis (PCA) at different time intervals with treated and untreated sera at 56 degrees C. The findings suggest the presence of reaginic antibodies, IgE being the major antibody as detected by enzime linked immunosorbent assay (ELISA). The MAG was subsequently fractionated using Sephandex G-100 and the fractions thus obtained (FI,FII and FIII) were used to challenge mice immunized with MMAG. It was found that FI was the only fraction which revealed an ITH similar to that revealed by MAG. The effect of infection with Trypanosoma cruzi on the autoimmune response to MAG was analyzed with different mouse groups intraperitoneally treated with 2 x 10(3) blood trypomastigotes/animal at several time intervals: namely, on days -5, 0, +5 and +10 with respect to the immunization with MMAG. The autoimmune response to MAG showed suppression when the animals received the parasites on the same day as the autoantigen.

Adjuvants, Immunologic↗
PubMed2006

Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride.

Dichloroacetyl chloride (DCAC) is formed from trichloroethene (TCE), which is implicated in inducing/accelerating autoimmune response. Due to its potent acylating activity, DCAC may convert proteins to neo-antigens and thus could induce autoimmune responses. Dichloroacetic anhydride (DCAA), which is a similar acylating agent, might also induce autoimmune responses. To evaluate if chloroacylation plays a role in the induction of autoimmunity, we have measured the autoimmune responses following treatment with DCAC or DCAA in autoimmune-prone MRL+/+ mice. Five-week-old female mice were injected intraperitoneally (twice weekly) with 0.2 mmol/kg of DCAC or DCAA in corn oil for 6 weeks. Total serum IgG, IgG1, and IgE levels were significantly increased in DCAC-treated mice as compared to controls. These increases corresponded with increases in DCAC-specific IgG and IgG1 levels. Total serum IgM was decreased in both DCAC- and DCAA-treated mice. Antinuclear antibodies, measured as an indication of systemic autoimmune responses, were increased in both DCAC- and DCAA-treated mice. Of eight Th1/Th2 cytokines measured in the serum, only IL-5 was significantly decreased in both treatment groups. The cytokine secretion patterns of splenic lymphocytes after stimulation with antibodies against CD3 (T cell receptor-mediated signal) and CD28 (costimulatory signal) differed between treatment and control groups. Levels of IL-1, IL-3, IL-6, IFN-gamma, G-CSF, and KC were higher in cultures of stimulated splenocytes from either DCAC- or DCAA-treated mice than from controls. The level of IL-17 was only increased in cultures from DCAC-treated mice. Increased lymphocytic populations were found in the red pulp of spleens following treatment with either DCAC or DCAA. In addition, thickening of the alveolar septa in the lungs of DCAC- or DCAA-treated mice was observed. The lung histopathology in exposed mice was consistent with the symptomology observed in welders exposed to DCAC/phosgene. Thickening was more pronounced in DCAC-treated mice. Our data suggest that DCAC and DCAA elicit autoimmune responses in MRL+/+ mice that might be reflective of their chloroacylation potential in vivo.

Acetates↗
PubMedDate not supplied

Experimental studies on genetically determined susceptibility to mercury-induced autoimmune response.

Individual differences in susceptibility may be caused by genetical as well as external variables. In mice as well as rats, autoimmune response can be induced by mercury or gold. The present data demonstrates that the autoimmune response depends qualitatively on the H-2 haplotype. If a strain of mice does not have the susceptible haplotype, no autoimmunity will be induced. However, even among the responding strains significant differences were observed. A clear correlation exists between renal mercury deposition and the autoimmune response in susceptible strains of mice. There was a threshold for induction of the autoimmune response in genetically susceptible mice. When exposure was interrupted, the mercury deposition decreased as did the antinucleolar antibody titre. Thresholds exist within susceptible strains below which no autoimmune response is induced.

Animals↗
PubMed2005

Reduced semen quality in chronic prostatitis patients that have cellular autoimmune response to prostate antigens.

BACKGROUND: The relationship between chronic prostatitis and fertility has been controversial for many years. We have previously shown the presence of a cellular autoimmune response against prostate antigens in a group of chronic prostatitis patients. Our main goal was to investigate whether chronic prostatitis (either caused by an infection or an autoimmune response to the prostate gland) could have a deleterious effect on semen quality. METHODS: Forty-four patients diagnosed as suffering from chronic prostatitis were included and divided into groups according to the presence of infection and/or cellular autoimmune response against prostate antigens. Healthy normal individuals were included as controls. Measurements for sperm concentration, motility, morphology, prostate and seminal vesicle markers, antisperm antibodies, white blood cells and pro-inflammatory cytokines were performed accordingly. RESULTS: The most severe abnormalities were seen in patients with no evident infection and an autoimmune response against prostate antigens. Moreover, significantly increased levels of pro-inflammatory cytokines were detected in seminal plasma from these patients. CONCLUSIONS: This study shows that chronic prostatitis patients with cellular autoimmune response to prostate antigens present important alterations in their semen quality parameters. We speculate that an autoimmune response against prostate antigens and the inflammatory process involved may affect male fertility.

Adult↗
PubMed2005

Assessment of autoimmune responses associated with asbestos exposure in Libby, Montana, USA.

Systemic autoimmune responses are associated with certain environmental exposures, including crystalline particles such as silica. Positive antinuclear antibody (ANA) tests have been reported in small cohorts exposed to asbestos, but many questions remain regarding the prevalence, pattern, and significance of autoantibodies associated with asbestos exposures. The population in Libby, Montana, provides a unique opportunity for such a study because of both occupational and environmental exposures that have occurred as a result of the mining of asbestos-contaminated vermiculite near the community. As part of a multifaceted assessment of the impact of asbestos exposures on this population, this study explored the possibility of exacerbated autoimmune responses. Age- and sex-matched sets of 50 serum samples from Libby and Missoula, Montana (unexposed), were tested for ANA on HEp-2 cells using indirect immunofluorescence. Data included frequency of positive tests, ANA titers, staining patterns, and scored fluorescence intensity, all against known controls. Serum immunoglobulin A (IgA), rheumatoid factor, and antibodies to extractable nuclear antigen (ENA) were also tested. The Libby samples showed significantly higher frequency of positive ANA and ENA tests, increased mean fluorescence intensity and titers of the ANAs, and higher serum IgA, compared with Missoula samples. In the Libby samples, positive correlations were found between ANA titers and both lung disease severity and extent of exposure. The results support the hypothesis that asbestos exposure is associated with autoimmune responses and suggests that a relationship exists between those responses and asbestos-related disease processes.

Asbestos↗
PubMed1982

Delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self antigens: a suggestive model of autoimmune response.

Previous studies suggested that trinitrophenyl (TNP)-modified syngeneic red cells induced humoral autoimmune response in mice with defective T cell function but not in normal mice. The ability of modified self antigen to induce autoimmune response in immunodeficient mice was further explored using the delayed-type hypersensitivity (DTH) as an assay system. Mice were immunized with syngeneic TNP-modified spleen cells (TNP-SC) and challenged by syngeneic nonmodified concanavalin A (Con A) or lipopolysaccharide (LPS)-stimulated spleen cells injected into their footpads. The DTH response was assessed 24, 48 and 72 h later by measuring the footpad swelling and was transferred to naive recipients with enriched T cells from TNP-SC-immunized irradiated A mice but not with serum or non-T cells. Adult thymectomized, X-irradiated (250 rds) and cyclophosphamide-treated mice injected with syngeneic TNP-SC generated a DTH response when subsequently challenged with syngeneic lymphoblasts (induced with Con A or LPS) but not when challenged with allogeneic blast cells. In contrast, normal mice treated in a similar manner exhibited a much less significant DTH response. SC incubated 1 to 3 h with Con A failed to elicit the DTH response of immunodeficient mice previously injected with TNP-SC. Both lymphoblasts that were induced in vitro with Con A diluted in fetal calf serum or in normal mouse serum-containing media, and lymphoblasts that were induced in vivo by interleukin 2 elicited DTH responses in X-irradiated, TNP-SC immunized mice. The syngeneic DTH response of the immunodeficient mice injected with TNP-SC was abrogated when they were simultaneously transplanted with syngeneic SC or nylon wool-passed syngeneic SC. If the transplanted splenocytes had been treated with anti-Thy-1 antiserum and complement they failed to abrogate the syngeneic-DTH response of the above mentioned mice. This result suggests that suppressor cells are programmed to control the autoimmune response induced with modified self antigens.

Animals↗
PubMed1984

Auto-delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self-antigens. II. Suppressor T cells control the autoimmune response.

The control of the autoimmune response to modified self-antigens was explored, using immunodeficient mice injected with syngeneic trinitrophenylated spleen cells (TNP-SC) as an experimental model system. X-irradiated (250 rad) A mice injected with TNP-SC and footpad-challenged 7 to 14 days later with syngeneic lymphoblasts generated a delayed-type hypersensitivity (DTH) response that was expressed by footpad swelling measured 24 h, 48 h and 72 h later. Histopathological examination showed massive inflammatory infiltration in the soft tissues of the limbs with extensive necrosis. This was not observed in X-irradiated mice that received the lymphoblast challenge only. The immunological activity was transferred from the X-irradiated TNP-SC-immunized mice to naive recipients by T cells (Lyt-1+) and not by serum, thus excluding the possibility that the inflammatory reaction is mediated by antibodies. We have previously presented evidence that the differentiation status of the lymphoblasts, and not contaminants from the incubation media, was the determinant factor eliciting the DTH response of immunodeficient mice injected with TNP-SC. Since only syngeneic lymphoblasts were able to elicit the DTH response of immunodeficient mice injected with syngeneic TNP-SC, we suggested that immunological activity was directed against self-antigens, thus expressing an autoimmune reactivity. The ability of immunodeficient mice to generate syngeneic DTH was not restricted to the TNP hapten or to inbred A-strain mice. X-irradiated BALB/c mice injected with syngeneic penicillinated spleen cells and challenged with syngeneic lymphoblasts generated a significant DTH response, in contrast to X-irradiated BALB/c mice exposed to the challenge dose only. X-irradiated A mice injected with syngeneic TNP-SC and simultaneously reconstituted with syngeneic splenocytes failed to generate a DTH response after the lymphoblast challenge, indicating that the syngeneic DTH response is controlled by normal suppressor cells. The suppressor cells were characterized as T cells carrying I-Jk, Lyt-1+, Lyt-2+ and Lyt-3+ antigenic markers. The suppressor cells abrogated the syngeneic DTH response of immunodeficient mice injected with TNP-SC, even when transferred a few days after the induction of immunological activity, but not when transferred 1 h before the lymphoblast challenge, indicating that even the established immunological activity can be restrained. Various immunological aspects of these observations and the significance of the findings in illuminating human autoimmune disorders are considered.

Animals↗
PubMed2004

Autoimmune response to proteins of proliferating cell nuclear antigen multiprotein complexes in patients with connective tissue diseases.

OBJECTIVE: To analyze the autoimmune response to the proliferating cell nuclear antigen (PCNA) multiprotein complex in patients with connective tissue diseases (CTD). METHODS: The PCNA complex was purified by affinity chromatography using anti-PCNA monoclonal antibodies. Then 196 serum samples from patients with systemic lupus erythematosus (SLE) and 82 from patients with other CTD were tested for reactivity with the complex by immunoblotting. RESULTS: Of 196 SLE sera, 61 (31%) reacted with at least one component of the PCNA complex, and most reactive sera contained autoantibodies to several components of the complex. Autoantibodies to PCNA complex were less common in patients with other CTD, and most of their sera reacted only with one or a few proteins in the complex. Two out of 20 scleroderma sera reactive with 100, 85, and 70 kDa proteins in the PCNA complex also had autoantibodies to topoisomerase I (topo I) antibodies, which is an element of the complex. These findings suggest that the autoimmune response to the PCNA complex was specific for SLE. Anti-PCNA complex antibodies were associated with an increased serum level of PCNA detected by ELISA. The spreading of the autoimmune response to the elements of the complex was observed in parallel with the increased serum PCNA level when a series of sera from a lupus patient were tested longitudinally. In addition, anti-PCNA complex antibodies were significantly correlated with lupus erythematosus cells. CONCLUSION: The "antigen-drive" system may play a crucial role in inducing the autoimmune response to the PCNA complex in patients with SLE.

Autoimmunity↗
PubMed2006

Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response.

Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity.

Aldehydes↗
PubMed2002

The genotype of mice influences the autoimmune response to spliceosome proteins induced by cytomegalovirus gB immunization.

In previous studies we have established a link between cytomegalovirus (CMV) infection and an autoimmune response to the U1-70 k protein of the spliceosome in man. This autoimmune response, generally referred to as the anti-RNP (ribonucleoprotein) antibodies, is observed in about 30% of patients with systemic lupus erythematosus (SLE). We have also found that the CMV glycoprotein B (CMV gB) when expressed in a adenovirus vector (Ad) could induce a significant anti-U1-70 k antibody response in several strains of mice, such as C3H, MRL and BALB/c. In the present study we examined the autoimmune response induced by immunization with Ad-gB in A/J and C57BL/6 (B6) mice and determined whether there was any autoimmune phenotype similar to that observed in patients with SLE. Thus groups of A/J and B6 mice were immunized with Ad/gB or with Ad alone and then observed for possible skin or kidney disease. In addition the autoantibody response to the spliceosome was measured, and the target antigens identified by immunoblot techniques. All of the A/J mice mounted a very high IgG response primarily to the U1-70 k protein of the spliceosome, with evidence of a rapid spreading of the autoantibody response to other components of the complex. In contrast, B6 mice mounted only a very low titre autoantibody response and failed to show signs or symptoms of autoimmunity. The A/J but not the B6 mice were found to have deposits of IgG in their kidneys, which were consistent with abnormal levels of blood urea nitrogen in the A/J but not B6 mice. This study demonstrates the importance of the genetic background in the susceptibility to autoimmunity.

Adenoviridae↗
PubMed2000

Trichloroethylene accelerates an autoimmune response by Th1 T cell activation in MRL +/+ mice.

Trichloroethylene (1,1,2-trichloroethene) is a major environmental contaminant. There is increasing evidence relating exposure to trichloroethylene with autoimmunity. To investigate potential mechanisms, we treated the autoimmune-prone MRL +/+ mice with trichloroethylene in the drinking water at 0, 2.5 or 5.0 mg/ml and sacrificed them at 4, 8 and 22 weeks. As early as 4 weeks of treatment, Western blot analysis showed a dose-dependent increase in the level of trichloroethylene-modified proteins, indicating that a reactive metabolite of trichloroethylene was formed. Significant increases in antinuclear antibodies (ANA) and total serum immunoglobulins were found following 4-8 weeks of trichloroethylene treatment, indicating that trichloroethylene was accelerating an autoimmune response. Investigation into possible mechanisms of this autoimmune response revealed that trichloroethylene treatment dramatically increased the expression of the activation marker CD44 on splenic CD4+ T cells at 4 weeks. In addition, splenic T cells from mice treated for 4 weeks with trichloroethylene secreted more IFN-gamma and less IL-4 than control T cells, consistent of a T-helper type 1 (Th1) type immune or inflammatory response. A specific immune response directed against dichloroacetylated proteins was found at 22 weeks of trichloroethylene treatment. Taken collectively, the results suggest that trichloroethylene treatment accelerated an autoimmune response characteristic of MRL +/+ mice in association with nonspecific activation of Th1 cells. In addition, long-term treatment with trichloroethylene led to the initiation of a trichloroethylene-specific immune response.

Animals↗