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N Fabien

Publications and source records attributed to N Fabien.

At least 19 recordsLinked to original sources
PubMed2002

Autoantibodies directed against ribosomal proteins in systemic lupus erythematosus and rheumatoid arthritis: a comparative study.

To assess the specificity of autoantibodies (aAbs) directed against the ribosomal P-proteins (RPPaAbs) in patients with systemic lupus erythematosus (SLE) and to investigate aAbs directed to other ribosomal proteins, 100 SLE, 100 rheumatoid arthritis (RA), 25 thyroiditis and 20 blood-donors were analyzed in a comparative study using an immunoblotting technique. Forty-eight percent of SLB sera contained aAbs directed against the ribosomal proteins of the 60 S subunit compared to 9% for RA, 5% for blood donors and 0% for thyroiditis. RPPaAbs were only found in SLE (25%) and aAbs directed to a 31 kDa and/or a 28 kDa protein of the 60 S subunit were found with a statistically higher frequency for SLE compared to RA (p < 0.0001). aAbs directed to proteins of the 40 S subunit were present in 63% of the SLE sera compared to 42% for RA, 4% for thyroiditis and 5% for blood donors. The number of positive sera was not statistically different between SLE and RA but a much more intense reactivity was observed for SLE sera. These data shows that the aAbs against the ribosomal proteins, especially the P-proteins along with the 28 and 31 kDa proteins of the 60 S subunit proteins, can be considered as useful biological markers for t he diagnosis of SLE inclinical practice.

Antibody Specificity↗
PubMed2001

[Auto-antibodies against acetylcholine receptors in myasthenia gravis].

USEFULLNESS OF DETECTION OF ANTIBODIES AGAINST THE ACETYLCHOLINE RECEPTOR IN THE DIAGNOSIS OF MYASTHENIA GRAVIS (MG): MG is an autoimmune disorder including a fatigability of skeletal muscles and the presence of antibodies against the acetylcholine receptor (AChRAbs). These Abs are pathogenic by blocking the acetylcholine receptor within the neuromuscular junction. A transient neonatal MG occurs in 12% of babies born to myasthenic mothers. AChRAbs have been found in 77 to 89% of systemic MG and in 47 to 60% in ocular form of MG. These Abs are generally directed against the "Main Immunogenic Region" (MIR) within the a subunit of the receptor; others are directed against beta, gamma and epsilon subunits. Eleven to 23% of the MG are negative for the Abs directed against the a subunit reinforcing the interest to detect the other AChRAbs, specially the anti-epsilon subunit Abs and the Abs directed against the muscle-specific receptor tyrosine kinase. MULTICENTER EVALUATION: In order to compare the results of AChRAbs for a same patient from various laboratories, a multicenter study was performed on 26 sera with different titers of AChRAbs using radioimmunoassays. Six french laboratories have participated to this study. The antigen was obtained from TE671 cells for 5 laboratories (3 used a commercial test) or from human muscle (1 laboratory). At the end of the study, the qualitative analysis of the results showed a concordance of 92.3%. The interpretation of AChRAbs assays can thus be done by clinicians whatever the test is used. A same quality control is nowadays used by the six laboratories in order to estimate quantitative results according to the assay performed. USEFULNESS OF THE OTHER ABS: The Abs directed against the striated muscle are good markers of thymoma in MG but are not specific for MG. The Abs directed against titin which is the major target of the anti-striated muscle Abs, are also good biological markers of thymoma specially in MG adults younger than 60 years. The detection of anti-myoid cells and thymic reticuloepithelial cells Abs is no more useful due to a lower sensitivity compared to the Abs directed against the striated muscle.

Autoantibodies↗
PubMed2001

Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients.

BACKGROUND: Antibodies to glutamic acid decarboxylase (GAD-Ab) are described in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in stiff-man syndrome, and, recently, in a few patients with cerebellar ataxia. OBJECTIVES: To show a link between GAD-Ab and some patients with cerebellar ataxia and to clarify their clinical and immunologic profiles. METHODS: Serum samples were selected from 9000 samples of 4 laboratories. The selection criterion was an immunohistochemical pattern compatible with GAD-Ab that was confirmed by radioimmunoassay. We identified 22 patients with stiff-man syndrome and 14 with cerebellar ataxia and GAD-Ab. RESULTS: Thirteen of the 14 patients with cerebellar ataxia and GAD-Ab were women, and 11 had late-onset IDDM. Patients did not have clinical or radiologic evidence of brainstem involvement. Ten patients had oligoclonal IgG bands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was observed in 5 of the 6 patients studied. The level of GAD-Ab of these patients was similar to those with stiff-man syndrome and significantly higher than those with IDDM or with polyendocrine autoimmunity (P<.001). However, the GAD-Ab levels of 6 of the 9 patients with polyendocrine autoimmunity overlapped with those of patients with cerebellar ataxia. CONCLUSIONS: These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.

Adult↗
PubMed2001

Lupus nephritis in a child with AIDS.

Concomitant acquired immunodeficiency syndrome (AIDS) and lupus nephritis is an exceptional feature in white patients. A white boy with maternofetal human immunodeficiency virus (HIV) infection had no medical follow-up until he presented at 12 years of age with a nephrotic syndrome, macrohematuria, renal failure, pancytopenia, and low CD4(+) cell count. A renal biopsy revealed severe lupus nephritis (World Health Organization class IV) with specific immune deposits in the absence of any clinical sign of systemic lupus erythematosus or specific autoantibodies at the time of diagnosis. The treatment consisted of methylprednisolone pulses followed by oral prednisone; antiretroviral triple therapy was started a few weeks later, which contributed to clinical and biologic improvement. To our knowledge, this is the first case report of lupus-like nephritis in a white child with AIDS, whose outcome might be improved significantly by a combination of steroids and antiretroviral therapy.

AIDS-Associated Nephropathy↗
PubMed2000

The clinical usefulness of the measurement of cytokines.

The utilization of accurate and sensitive methods for the measurement of cytokines in body fluids is prerequisite for the proper use of these mediators in clinical practice. Many factors contribute to the complexity of cytokine quantitation. Bioassays historically preceded immunoassays, which are now very popular, but there is a need for standardization. Nevertheless, due to the local effects of cytokines, the study of their blood levels is of limited value for an understanding of the pathophysiology of these mediators. This explains the development of alternative approaches to assess the ability of cells to produce cytokines. These include the Enzyme-Linked Immuno Spot Assay (ELISPOT), the measurement of cell-associated cytokines by flow cytometry, and the study of cytokine secretion by isolated peripheral blood mononuclear cells or by whole blood test. All these techniques, associated with a local detection of cytokines by immunohistochemistry or in situ hybridization and reverse transcriptase polymerase chain reaction, appear to be complementary tools for a better understanding of the biology of cytokines. Selected examples of possible clinical applications related to infectious diseases, cancer, autoimmune diseases, allergy, transplantation and preclinical evaluation of drugs and biotechnology products are given.

Body Fluids↗
PubMed1999

Autoantibodies directed against the ribosomal P proteins are not only directed against a common epitope of the P0, P1 and P2 proteins.

The autoantibodies (aAbs) directed against the ribosomal P proteins (RPP aAbs) are known to react mainly against epitopes localized within the common C-terminal sequence of the three acidic ribosomal P proteins, P0, P1 and P2. In order to investigate the opportunity to select short recombinant peptides of this common C-terminal sequence to detect the RPP-aAbs, the location of the epitopes recognized by ribosomal proteins (RP) aAb(+)sera of systemic lupus erythematosus patients (SLE) was investigated. Immunoblotting and ELISA techniques using extracted or recombinant, entire or cleaved RPP showed that 55% of the RP aAbs were directed against the three ribosomal P0, P1, and P2 proteins. The epitopes recognized by the RPP aAbs are located not only within the C-terminal sequence common to the three proteins but also within the N-terminal sequence of the P2 or P1 protein. The other RP aAbs sera (45%) did not react with all three proteins but with some of them, and showed the following pattern: P0(+)P1(+); P1(+); P2(+); P0(+)and P1(+). They recognized epitopes located in the region of the C-terminal sequence of the protein but not common to the three proteins. In addition two out of the six monoclonal Abs produced by immunization of mice using the P1 protein did not react with the peptide N-65 or N-71 of the P2 protein or with the C-terminal sequence of the three proteins. In conclusion, this study showed that the RPP aAb in SLE patients are not only directed against epitopes within the C-terminal sequence shared by the three acidic ribosomal P proteins. In view of these data it seems necessary to be cautious in using only a C-terminal peptide of ribosomal P proteins in tests performed to detect RPP aAb in human sera.

Amino Acid Sequence↗
PubMed1999

Multicenter evaluation study on a new HEp2 ANA screening enzyme immune assay.

The COBAS Core HEp2 ANA enzyme immune assay (EIA) was evaluated in a precision and a clinical sample study in comparison to indirect immunofluorescence assay (IFA) on HEp2-cells. In the precision study the COBAS Core EIA yielded intraassay coefficient variations (CVs) mostly below 9%, and interassay CVs between 4.7% and 10.4%. When comparing the COBAS Core EIA to IFA, the results corresponded well in healthy subjects, systemic lupus erythematosus, mixed connective tissue disease and rheumatoid arthritis. In the case of Sjögren's syndrome and scleroderma patients the COBAS Core EIA yielded a lower rate of positive results compared to IFA. This discrepancy may be explained by the lack of detection of autoantibodies to nuclear antigens that can be identified only by IFA due to their compartmentalization and higher localized antigen density in HEp2 cells. The discrepancies in the group of dermato/polymyositis patients are due to the fact that the EIA contains mainly nuclear antigens and was able to detect only antibodies against the cytoplasmic Jo1 antigen that was added to the HEp2 nuclear extract. Routine sera were also evaluated; good agreement was found in sera from patients attending tertiary reference centres for autoimmune diseases but a higher number of discrepancies was reported in sera from unselected populations.

Adult↗
PubMed1998

Cytokine assays in human sera and tissues.

The use of accurate and sensitive methods for the measurement of cytokines in body fluids is an absolute prerequisite for the proper use of these mediators in clinical practice. Many factors contribute to the complexity of cytokines quantitation: these molecules circulate at very low levels (e.g. pg/ml) under various molecular forms, the existence of circadian rhythms has been described, and the presence of inhibitors (binding proteins, soluble receptors, autoantibodies) can potentially interfere in the assays. Blood collection for cytokines needs particular attention to prevent possible contamination by endotoxins, which can trigger cytokines cellular production after sampling. Bioassays historically preceded immunoassays; the latter techniques are now very popular, but there is an urgent need for standardisation between the different kits commercially available. Nevertheless, due to the essentially local effects of cytokines, the study of their circulating levels only represents the 'tip of the iceberg' and is of limited value for a global understanding of the pathophysiology of these mediators. This explains the development of other approaches to assess the ability of cells to produce cytokines. These include the ELISPOT assay, the measurement of cell-associated cytokines by flow cytometry, and the study of cytokine secretion by isolated peripheral blood mononuclear cells or by whole blood test. All these techniques, associated with a local detection of cytokines by immunohistochemistry or in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR), appear to be complementary tools for a better understanding of the multiple aspects of the biology of cytokines.

Biological Assay↗
PubMed1998

Protection against autoimmune diabetes with oral insulin is associated with the presence of IL-4 type 2 T-cells in the pancreas and pancreatic lymph nodes.

Oral administration of antigens has been proposed in the prevention and treatment of autoimmune diseases. We reported that oral administration of 0.8 mg of recombinant human insulin to 6-week-old NOD mice every other day for a month generated regulatory T-cells that were able to reduce the severity of insulitis and the percentage of clinical diabetes in naive irradiated recipients when co-injected with diabetogenic T-cells. In the present study, immunohistochemical analysis of the pancreatic glands revealed that injection of T-cells from insulin-fed mice upregulated the number of interleukin (IL)-4-secreting cells within the islets. Using two strains of NOD mice congenic at the Tbeta, or Thy1, locus, we observed a higher proportion of T-cells from insulin-fed mice in both the spleen (7.73 +/- 0.3 vs. 5.57 +/- 0.2%; P < 0.001) and the pancreatic lymph nodes (10.1 +/- 0.8 vs. 7.2 +/- 0.7%; P < 0.05) of cotransferred mice. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, mice reconstituted with T-cells from insulin-fed animals had detectable amounts of IL-4 mRNA, specifically in the pancreatic lymph nodes (8 of 9 experimental mice vs. 1 of 9 control mice) and the pancreas (3 of 3 experimental mice vs. 0 of 3 control mice). Gamma-interferon mRNA was detectable in all cotransferred animals, but IL-10 mRNA and transforming growth factor beta mRNA were undetectable. These results suggested a shift from a T-helper 1 (Th1) to a Th2 pattern of cytokine expression and underlined the role of pancreatic lymph nodes in the protection. Repeated injections of 500 microg s.c. of anti-IL-4 monoclonal antibody led to an accentuation of the severity of islet infiltration and to the development of clinical diabetes. We concluded that oral administration of insulin can induce the presence of regulatory T-cells in the pancreas and the corresponding draining lymph nodes, initiate the secretion of IL-4 in this microenvironment sufficiently to suppress the activity of Th1 autoreactive T-cell clones, and ultimately provide protection against autoimmune diabetes.

Administration, Oral↗
PubMed1997

A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes.

Mucosally induced immunological tolerance is an attractive strategy for preventing or treating illnesses resulting from untoward inflammatory immune reactions against self- or non-self-antigens. Oral administration of relevant autoantigens and allergens has been reported to delay or suppress onset of clinical disease in a number of experimental autoimmune and allergic disorders. However, the approach often requires repeated feeding of large amounts of tolerogens over long periods and is only partly effective in animals already systemically sensitized to the ingested antigen such as in animals already harboring autoreactive T cells, and thus presumably also in humans with an autoimmune disease. We have recently shown that oral administration of microgram amounts of antigen coupled to cholera toxin B subunit (CTB), can effectively suppress systemic T cell reactivity in naive as well as in immune animals. We now report that feeding small amounts (2-20 microg) of human insulin conjugated to CTB can effectively suppress beta cell destruction and clinical diabetes in adult nonobese diabetic (NOD) mice. The protective effect could be transferred by T cells from CTB-insulin-treated animals and was associated with reduced lesions of insulitis. Furthermore, adoptive co-transfer experiments involving injection of Thy-1,2 recipients with diabetogenic T cells from syngeneic mice and T cells from congenic Thy-1,1 mice fed with CTB-insulin demonstrated a selective recruitment of Thy-1,1 donor cells in the peripancreatic lymph nodes concomitant with reduced islet cell infiltration. These results suggest that protection against autoimmune diabetes can be achieved by feeding minute amounts of a pancreas islet cell autoantigen linked to CTB and appears to involve the selective migration and retention of protective T cells into lymphoid tissues draining the site of organ injury.

Administration, Oral↗
PubMed1996

Active suppression of diabetes after oral administration of insulin is determined by antigen dosage.

We have previously demonstrated that feeding six-week-old female mice with 20 units of human insulin every 2 - 3 days for 15 or 30 days induced an active mechanism of suppression through the generation of regulatory T cells that reduced the number of successful diabetic transfers in irradiated NOD recipients. In the present study, we analyzed the effects of antigen dosage and the critical period of cell injection to obtain protection. The effects of the dose of insulin feeding were therefore compared during cotransfer experiments of 5 x 10(6) T cells from diabetic mice and 5 x 10(6) T cells from the spleen of mice receiving 10 units, 20 units, or 40 units of insulin or saline every 2 - 3 days for 15 days. Only T lymphocytes from mice fed with 20 units conferred active cellular protection during adoptive transfer with a significant delay in diabetes onset (p = 0.002). No significant difference was noticed during histological analysis of pancreatic glands, indicating tha insulitis was not prevented. However, mice receiving T lymphocytes from the 20 units of insulin-fed animals had a milder form of inflammation, with a significantly lower percentage of severely infiltrated islets. Injecting regulatory T cells 7 days and 14 days after iv injection of diabetogenic T cells did not modify the incidence curves of diabetes in the recipients, suggesting that cellular interactions and delay in cell trafficking were determinants. These results may have important clinical implications in humans. In conclusion, this study indicates the importance but also the limits of antigen therapy in type I diabetes. Antigen dosage is a critical element for active suppression. Such analysis is important to perform in humans before the initiation of a large-scale prevention trial in prediabetic individuals.

Administration, Oral↗
PubMed1996

Low frequency of p53 mutations in human thyroid tumours; p53 and Ras mutation in two out of fifty-six thyroid tumours.

OBJECTIVE: p53 is a well-known nuclear phosphoprotein encoded by a suppressor gene know to be mutated in various kinds of human tumours. A relationship between p53 gene mutation and tumour progression seems to be a common feature of several neoplasias. DESIGN: In order to investigate the role of p53 mutations in human thyroid tumours, DNA samples derived from fifty-six neoplastic tissues, ranging from benign adenomas to undifferentiated carcinomas, were examined for the presence of p53 gene mutations. METHODS: The analysis has been conducted using polymerase chain reaction (PCR) amplification of the exons 5-9 of the p53 gene followed by single strand conformation polymorphism (SSCP) and sequence analyses. RESULTS: One anaplastic carcinoma and one papillary carcinoma showed p53 gene mutations in exons 5 and 8, respectively. A cell line established from the papillary carcinoma showed the same mutation present in the original tumour. Both p53 mutations were heterozygous. The p53 positive samples were analysed for other genetic alterations frequently detected in human thyroid carcinomas (mutations of the RET, TRK, and ras oncogenes): both p53-mutated samples proved to be mutated at level of codon 13 of the c-Ki-ras gene. CONCLUSIONS: Our data confirm that p53 gene alterations are rare in well-differentiated thyroid tumours, that they are an important requirement for the establishment in culture of human thyroid carcinoma cell lines, and that they can be associated with other genetic alterations, namely ras mutations, in the malignant progression of thyroid tumours.

Base Sequence↗
PubMed1996

Lymphocyte function associated antigen-1, integrin alpha 4, and L-selectin mediate T-cell homing to the pancreas in the model of adoptive transfer of diabetes in NOD mice.

The involvement of adhesion molecule in the process of T-cell homing to the pancreas was investigated in the model of the T-cell transfer of type I diabetes in NOD mice. Treatment of mice using monoclonal anti-lymphocyte function associated antigen (LFA)-1, anti-integrin alpha 4, anti-intercellular adhesion molecule (ICAM)-1, and anti-L-selectin antibodies (monoclonal antibodies [mAbs]) gave rise to a partial or complete prevention of diabetes via different mechanisms of protection. On day 20 posttransfer, diabetes was only observed in control mice (26 of 32) and in few mice treated with the anti-L-selectin mAbs (3 of 24). On day 60, the best protection was observed using the anti-LFA-1 or the anti-integrin alpha 4 mAbs with 3 of 11 and 2 of 5 diabetic mice, respectively. On day 20, no insulitis was observed in the pancreases of mice treated with these mAbs compared with the pancreases of controls, suggesting that such treatment blocked the penetration of T-cells into the islets. In vitro adhesion assays confirmed that adhesion of T-cells to the pancreatic endothelium was blocked, except when using the anti-L-selectin mAb, which induced a modification of the traffic of the transferred T-cells; the ability of T-cells to migrate into the pancreatic lymph nodes was significantly reduced (10.4 vs. 22%). Anti-LFA-1 mAbs did not modify such T-cell trafficking. The present study, therefore, elucidates the role of LFA-1, integrin alpha 4, and L-selectin in T-cell homing to the pancreas, first step of the cascade of events leading to type I diabetes.

Animals↗
PubMed1996

[Evaluation of the role of cytology in the diagnosis of cancer of the lung. Comparison between cytology and pathological anatomy in 330 cases of proximal cancers].

This retrospective study was performed to evaluate the interest of cytology in the diagnosis of pulmonary carcinomas. Bronchial samples were collected from 330 patients known to display a macroscopic lesion which was detected by bronchoscopy. Cytological analysis of the bronchial brushings and washings, removed at the first fibroscopy, allowed the diagnosis of malignancy in 92% of the cases analyzed whereas the biopsy confirmed the malignancy in 77% of the cases. In conclusion cytological studies gave information on malignity and classification in 90% of the cases. However histological classification only could guarantee the choice of the best treatment regimen.

Adenocarcinoma↗
PubMed1996

Effects of insulin like growth factor-1 and insulin on effector T cells generating autoimmune diabetes.

To compare the protective effects of IGF-1 and insulin on the autoimmune process of beta-cell destruction, permissive NOD recipients were adoptively transferred with 7 x 10(6) autoreactive T cells from diabetic NOD mice and then administered either 10 micrograms of rhIGF-1 or 0.5 unit of regular insulin subcutaneously twice daily for three weeks. The final incidence of successful transfers of diabetes observed at day 22 was significantly reduced in 1/12 mice (8.3%) treated with IGF-1, while diabetes was observed in 4/10 (40%) receiving insulin and 7/11 (63.4%) controls. A marked reduction of insulitis during histological analysis of the pancreatic glands of IGF-1 or insulin-treated mice was also observed. Non-diabetic mice treated with rhIGF-1 had a higher mean +/- SD percentage of intact islets (68.9 +/- 36% vs 10.7 +/- 13%, p < 0.01) and a lower percentage of severely infiltrated islets (5.7 +/- 9.8% vs 30.3 +/- 21%) than non-diabetic control mice. Insulin reduced islet-cell infiltration, though to a lesser extent, with a high percentage of normal islets (55.2 +/- 31%, p < 0.02). Some mice developed diabetes and severe islet-cell infiltration despite rhIGF-1 or insulin, thus indicating that some committed T cells were still able to invade islets and cause beta-cell destruction. To evaluate the effects of rhIGF-1 and insulin on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1, 2 mice injected into congenic NOD-N Thy-1, 1 mice were monitored three weeks after adoptive cell transfer. The percentage of Thyq-1.2+ T cells was significantly reduced in the spleen (10.8 +/- 1.3% vs 17.2 +/- 3.9%, p = 0.004) of rhIGF-1 treated mice as compared to the thymus (68.4 +/- 7.9% vs 72.87 +/0 6.2, p = 0.306). Similar experiments performed in mice treated with insulin revealed no significant differences in the percentages of Thy-1,2+ T cells compared to controls in the spleen (l4.3 +/- 1.4%), thymus (84 +/- 2.5%) or pancreatic lymph nodes (21.5 +/- 1.6% vs 23.4 +/- 1.5%) of treated animals. These results suggest that rhIGF-1, as compared to insulin, could influence T-cell trafficking to the lymphoid organs in addition to affecting beta cells. These findings may have important implications for new preventive strategies in human Type 1 diabetes mellitus.

Animals↗
PubMed1996

Transgenic mice carrying the human KRAS oncogene under the control of a thyroglobulin promoter: KRAS expression in thyroids analyzed by in situ hybridization.

We have previously generated transgenic mice bearing a molecular construct obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras oncogene (KRAS). These mice showed thyroid abnormalities, although at very low incidence and after a long latency period. A six-month thyrotropin (TSH) stimulation of thyroid glands, followed by a two-month suspension, induced a significant increase in the number of lesions in transgenic mice as compared with a nontransgenic control group. Our goal was to follow the progression and the reversion of the tumorigenesis process in relationship with the levels of expression of the KRAS in this experimental model. In situ hybridization was used to detect expression of KRAS mRNA in sections of thyroids of the various groups of mice. A positive hybridization was observed in follicular cells of TSH-stimulated transgenic mice, whereas no expression could be appreciated in control nontransgenic mice. A positive signal was also observed in thyroid glands excised from transgenic mice after the 2-month suspension of treatment; however, the number of expressing cells was decreased compared with transgenic mice killed immediately after 6 months of a goitrogen regimen. Finally, every cell in the single thyroid carcinoma observed after the two-month suspension was positive for the transgene mRNA. This study further strengthens the role of the expression of mutated KRAS in the early stages of thyroid follicular cell transformation and indicates that when the expression of the mutated KRAS becomes independent of exogenous TSH stimulation, this event coincides with a further progression towards tumorigenesis.

Adenoma↗
PubMed1995

Pancreatic lymph nodes are early targets of T cells during adoptive transfer of diabetes in NOD mice.

The circulation pathway of diabetogenic T lymphocytes prior to insulitis was investigated using adoptive transfer of diabetes in the non-obese diabetic (NOD) mouse model. Transferred T cells were distinguished from recipient T cells using two strains of mice congenic at the Thy1 locus. They were monitored in the pancreas and in several lymphoid organs including thymus, spleen, and lymph nodes from pancreatic, mesenteric, axillary, inguinal and lomboaortic areas, from Day 0 to Day 15 after the adoptive lymphocytic transfer. Immunohistochemical studies showed that at Day 2 post-transfer the pancreatic lymph nodes (PLN) and to a lesser extent the spleen, are the first two organs to be infiltrated. The amount of T cells of donor origin using quantitative flow cytometric analysis was 4% and 2.6% respectively. This percentage increased to 19% in the PLN at Day 15 and did not exceed 7% in the spleen. Analysis of the expression of IL-2 receptor present at the surface of activated T lymphocytes showed that 73% of donor T cells were activated in the PLN within 3 days post-transfer in contrast to 0% in the spleen. The accumulation and activation of T cells in the PLN may imply a role of these lymphoid organs in harbouring the diabetogenic T cells during the early steps of the disease.

Animals↗