RESUMO
Autoantibodies against the muscle acetylcholine receptor (AChR) play an essential role in the pathophysiology of autoimmune myasthenia gravis (MG). Their serum titers, however, vary considerably among patients. Our aim was to investigate whether their variation might be explained by genetic factors. Using different methods, we have obtained strong evidence for a three-locus association influencing autoantibody titers in MG patients with thymus hyperplasia or with a normal thymus. Two of the loci, one encoding the AChR alpha-subunit, the other encoding the alpha-chain of the class II antigen-presentation molecule, HLA-DQ, demonstrated interaction to determine high autoantibody titers. The third locus was associated with the 8.1 ancestral HLA haplotype. It exerted an additive effect and it is postulated to have a nonantigen specific immunoregulatory function. Our study demonstrates for the first time that polymorphism of an autoantigen gene may quantitatively modify the immune response against it. Altogether, the data lend support to a three-gene model to explain autoantibody expression in a subset of MG patients.
Assuntos
Autoanticorpos/sangue , Autoantígenos/genética , Antígenos HLA-DQ/genética , Miastenia Gravis/genética , Receptores Colinérgicos/genética , Autoanticorpos/biossíntese , Autoanticorpos/genética , Autoantígenos/imunologia , Estudos de Casos e Controles , Antígenos HLA-DQ/imunologia , Cadeias alfa de HLA-DQ , Humanos , Repetições de Microssatélites/genética , Miastenia Gravis/etnologia , Miastenia Gravis/imunologia , Polimorfismo Genético/genética , Receptores Colinérgicos/imunologia , Timo/imunologia , Timo/patologia , População Branca/genéticaRESUMO
BACKGROUND: MG is an autoimmune disease of the neuromuscular junction. MG with thymus hyperplasia has been associated with, but not genetically linked to, the HLA-DR3 haplotype. OBJECTIVE: To re-evaluate the association of HLA with MG in 656 patients with generalized disease and to test linkage of HLA to MG with thymus hyperplasia. METHOD: Patients were genotyped for HLA-DRB1. Data analysis included case-control comparisons after subgrouping patients by thymus histopathology. The transmission of parental alleles to MG offspring with thymus hyperplasia was studied in simplex families using the transmission/disequilibrium test (TDT) as a test of linkage. RESULTS: MG with thymus hyperplasia was positively associated with DR3 (OR = 4.5, p = 1 x 10(-6)) and negatively associated with DR7 (OR = 0.28, p = 1 x 10(-6)), based on both case-control comparisons and TDT. No association was detected with thymomas. Conversely, patients who lacked thymus anomalies but expressed anti-titin antibodies (ATA) had an increase of DR7 (OR = 2.08, p = 4 x 10(-3)) and a decrease of DR3 (OR = 0.33, p = 9 x 10(-3)). CONCLUSIONS: The authors established linkage of HLA to MG and thymus hyperplasia, defining the MYAS1 locus. Moreover, DR3 and DR7, or closely linked genes, have opposing effects on MG phenotypes. Nonthymomatous patients with ATA may be a pathogenetically distinct subset of MG patients.
Assuntos
Antígeno HLA-DR3/genética , Desequilíbrio de Ligação , Proteínas Musculares/imunologia , Miastenia Gravis/genética , Miastenia Gravis/imunologia , Proteínas Quinases/imunologia , Adulto , Autoanticorpos/análise , Estudos de Casos e Controles , Conectina , Feminino , Heterogeneidade Genética , Genótipo , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Masculino , Miastenia Gravis/patologia , Fenótipo , Timo/patologia , Hiperplasia do Timo/genética , Hiperplasia do Timo/imunologia , Hiperplasia do Timo/patologiaRESUMO
HLA DRB1, DQA1 and DQB1 polymorphisms were analyzed by PCR-SSO typing in a sample of the Moroccan population from Souss. Uneven allelic frequency distributions are observed at each locus, with particularly high frequencies for DRB1*0701, DRB1*0301, DQA1*0501, DQA1*0201, and DQB1*0201. Only three haplotypes (DRB1*0701-DQA1*0201-DQB1*0201, DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*11-DQA1*0501-DQB1*0301) account for nearly 50% of the total gene frequencies. A genetic distance analysis reveals that the Moroccan population is close to the Spanish and the Algerians, who live in geographically neighboring areas. However, the Souss population is also characterized by a lower level of genetic diversity compared to other African and European populations from the Mediterranean area. This may be the result of a rapid genetic drift due to their likely geographical and/or cultural isolation.
Assuntos
Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Polimorfismo Genético , Alelos , DNA , Frequência do Gene , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Marrocos/etnologia , PopulaçãoRESUMO
The contribution of autoantibodies, HLA markers and age to long-term estimates of risk of type 1 diabetes were examined after a median of 11 years (range 7.5-14) during the follow-up in a cohort of 234 siblings (aged 2-29 years) of French children with recent-onset type 1 diabetes, of whom 12 (5.1%) developed diabetes. We evaluated islet cell antibodies (ICA) by indirect immunofluorescence and autoantibodies to insulin (IAA), to the 65 kDa isoform of glutamic acid decarboxylase (GADA) and to the IA-2 protein (IA-2A) by radioligand assay in sequential serum samples. Among the 234 siblings of type 1 diabetic patients screened, 27 were positive for at least one antibody, 11 of whom progressed to develop type 1 diabetes during the follow-up (sensitivity, 92%, predictive value, 41%). Among the four antibodies tested individually, ICA had the highest sensitivity (83%) but a poor predictive value (59%) and IA-2A the highest predictive value (70%). IAA and GADA both exhibited poor sensitivity and predictive value. Combinations of antibodies achieved better predictive values than antibodies tested individually. Satisfactory predictive values were obtained for the combination of GADA with IA-2A (83%), for any combination of at least two antibodies other than ICA (70%) and for the combination of ICA with at least one other antibody (69%). The risk estimates were highest in the presence of three or four antibodies, whether comprising ICA or not, but with a concomitant loss of sensitivity. For most antibody combinations, cumulative risks showed progression from approximately 50% after 5 years to 100% after 13 years. HLA-DR3/4 was significantly more frequent in siblings developing type 1 diabetes than in non-diabetic siblings (9/12 vs. 39/217, relative risk (RR)=14, P=0.0001). The predictive value of HLA-DR3/4 was low (19%); however, taking into account the presence of HLA-DR3/4 in subjects who were positive for more than one antibody resulted in a higher predictive value (67%, vs. 20% in non-DR3/4 subjects, P=0.02). In addition, siblings developing diabetes were younger at entry than those who did not (mean =7.5 +/-1.23 vs. 12.5 +/-0.39 years, respectively; P=0.01). Ten of 12 were aged less than 10 years compared with 106/222 non-diabetic siblings (RR =5.4, P=0.03). Moreover, younger age was associated with a more rapid development of type 1 diabetes. In conclusion, our results show that the combination of IAA, GADA and IA-2A autoantibodies in sequential serum samples is satisfactory for the identification of subjects at risk of developing type 1 diabetes. Additional factors such as younger age and HLA-DR3/4 as markers of progression to disease may contribute to more efficient prediction in antibody positive subjects.
Assuntos
Envelhecimento/fisiologia , Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/genética , Antígenos HLA/fisiologia , Adolescente , Adulto , Idoso , Envelhecimento/imunologia , Autoanticorpos/análise , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Feminino , Seguimentos , Glutamato Descarboxilase/imunologia , Antígenos HLA/imunologia , Humanos , Anticorpos Anti-Insulina/análise , Anticorpos Anti-Insulina/imunologia , Ilhotas Pancreáticas/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.
Assuntos
Antígenos de Diferenciação/genética , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 1/genética , Imunoconjugados , Polimorfismo Genético , Abatacepte , Alelos , Antígenos CD , Antígeno CTLA-4 , Estudos de Casos e Controles , Etnicidade/genética , Humanos , Desequilíbrio de Ligação , Repetições de MicrossatélitesRESUMO
HLA class II polymorphism in Moroccan IDDM patients has not been investigated so far. In this study, HLA-DRB1, -DQA1, and -DQB1 allele and haplotype frequencies were analyzed in 125 unrelated Moroccan IDDM patients and 93 unrelated healthy controls, all originating from the Souss region and mostly of Berber origin. Some common features with other Caucasian groups were observed, in particular, a predisposing effect of the DRB1*03-DQA1*0501-DQB1*0201 and DRB1*04-DQA1*0301-DQB1*0302 alleles or allelic combinations. The Moroccan IDDM group also presented with more specific characteristics. Among DRB1*04 subtypes, DRB1*0405 was associated with susceptibility to and DRB1*0406 with protection from the disease. The haplotype and the relative predispositional effect (RPE) analyses indicated that the DRB1*08-DQA1*0401-DQB1*0402 haplotype was also associated with susceptibility to IDDM. Interestingly, the DRB1*09-DQA1*0301-DQB1*0201 haplotype, completely absent from the control group and very rare in North African populations, was observed in 7.2% of the Moroccan diabetics. Conversely, the DRB1*07-DQA1*0201-DQB1*0201 and DRB1*15-DQA1*0102-DQB1*0602 haplotypes were associated with protection from IDDM. Finally, we observed an age-dependent genetic heterogeneity of IDDM, the frequencies of predisposing alleles being higher and those of protective alleles lower in childhood- than in adult-onset diabetics. Our data on Moroccan diabetics, together with data on European and Northern Mediterranean patients, suggest a gradient of various HLA class II predisposing and protective markers that link these populations.
Assuntos
Alelos , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-D/genética , Haplótipos/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA-D/análise , Humanos , Lactente , Marrocos/etnologia , Polimorfismo Genético/imunologiaRESUMO
Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV-infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers.
Assuntos
DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/sangue , Leucócitos Mononucleares/virologia , Portador Sadio/virologia , Distribuição de Qui-Quadrado , Hepatite B/genética , Antígenos da Hepatite B/sangue , Hepatite Crônica/virologia , Humanos , Leucócitos Mononucleares/classificação , Hibridização de Ácido Nucleico , Vasculite/virologiaAssuntos
Síndromes de Imunodeficiência/etiologia , Uremia/complicações , Linfócitos B/imunologia , Proteínas Sanguíneas/análise , Humanos , Síndromes de Imunodeficiência/imunologia , Interleucina-1/sangue , Interleucina-2/biossíntese , Ativação Linfocitária , Fagócitos/patologia , Receptores de Interleucina-2/análise , Diálise Renal/efeitos adversos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/análise , Uremia/imunologia , Uremia/terapiaRESUMO
The production and targeting of a major T cell derived lymphokine, Interleukin 2 (IL-2), were studied in 23 uremic patients undergoing regular hemodialysis treatment and 20 uremic patients prior to the onset of renal replacement therapy. In hemodialyzed patients, abnormally increased proportions of circulating T cells spontaneously expressing high affinity IL-2 receptors (IL-2 Rec) were detected: they bound a monoclonal antibody specifically directed to the IL-2 Rec 55 kDa chain (Tac antigen) (mean +/- SEM: 7.12 +/- 0.81% in patients vs. 2.15 +/- 0.39% in normal controls, P less than 0.0001) and significantly proliferated in presence of human recombinant IL-2 alone (mean +/- SEM: 5438 +/- 729 cpm in patients vs. 1647 +/- 244 cpm in normal controls). Hemodialyzed patients also exhibited significantly increased serum levels of soluble IL-2 receptor (mean +/- SEM: 4036 +/- 947 U/ml in patients vs. 253 +/- 29 U/ml in normal controls. P less than 0.001). Moreover, a significantly decreased IL-2 activity was detected in the supernatants of stimulated T cells from hemodialyzed patients (mean +/- SEM: 0.93 +/- 0.12 U/ml in patients vs. 2.49 +/- 0.22 U/ml in normal controls, P less than 0.0001). In nine hemodialyzed patients who were analyzed before and immediately after the hemodialysis session no acute modifications of the various parameters analyzed were detected. Although less profound, a similar pattern of T cell abnormalities was observed in the uremic non-hemodialyzed patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Interleucina-2/imunologia , Falência Renal Crônica/imunologia , Receptores de Interleucina-2/imunologia , Diálise Renal , Linfócitos T/imunologia , Adulto , Feminino , Imunofluorescência , Humanos , Falência Renal Crônica/terapia , Ativação Linfocitária/imunologia , MasculinoRESUMO
Thirteen patients with severe steroid-resistant or steroid-dependent forms of systemic lupus erythematosus were treated with cyclosporine (average dose 5 mg/kg/d) for an average period of 12 months. In eight patients the disease activity decreased, as substantiated by the reduction in the amount of steroid required to control the clinical manifestations. Interruption of cyclosporine treatment was associated with relapse or worsening of disease in five subjects. These favorable clinical results occurred in the absence of changes in the levels of antinuclear, anti-double-stranded deoxyribonucleic acid autoantibodies or plasma complement components; plasma IgG concentration increased significantly. Six patients had signs of moderate cyclosporine nephrotoxicity that disappeared when the administration of the drug was discontinued. Hypertension was the most serious side effect observed in eight subjects; in every case it was controlled by antihypertensive medicine. These data indicate that cyclosporine may be beneficial in the treatment of some patients with severe forms of systemic lupus erythematosus.
Assuntos
Ciclosporinas/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adolescente , Adulto , Autoanticorpos/análise , Ciclosporinas/efeitos adversos , Avaliação de Medicamentos , Resistência a Medicamentos , Feminino , Humanos , Hipertensão/induzido quimicamente , Nefropatias/induzido quimicamente , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêuticoRESUMO
We have tested the different mononuclear blood cell populations of seven patients with severe haemophilia and one patient with F VII deficiency for the presence of HBV DNA. These subjects were all polytransfused with non-heated coagulation factors; three were HBsAg positive, five HBsAg negative but anti-HBc and anti-HBs positive; HBV DNA sequences were detected in six subjects including three without detectable serum HBsAg. Furthermore the viral DNA sequences were identified in the T lymphocyte subpopulations (OKT4+ and/or OKT8+ cells). This observation suggests that HBV infection of lymphocytes might be related to the immunological disorders observed in these patients.
Assuntos
DNA Viral/análise , Hemofilia A/microbiologia , Vírus da Hepatite B , Linfócitos/microbiologia , Fatores de Coagulação Sanguínea/uso terapêutico , Feminino , Hemofilia A/complicações , Hemofilia A/terapia , Hepatite B/complicações , Humanos , Masculino , Linfócitos T/classificaçãoRESUMO
Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.
Assuntos
Ativação Linfocitária , Linfocinas/biossíntese , Diálise Renal , Linfócitos T/imunologia , Adulto , Linfócitos B/imunologia , Feminino , Substâncias de Crescimento/biossíntese , Humanos , Interleucina-2/biossíntese , Interleucina-4 , Linfocinas/farmacologia , Masculino , Receptores Imunológicos/análise , Receptores de Interleucina-2 , Linfócitos T/classificaçãoRESUMO
The proliferative response of highly purified human peripheral blood or tonsil lymphocytes in the presence of soluble protein A (SpA) was investigated. SpA was shown to be a potent mitogen for T lymphocytes from peripheral blood or tonsils. Conversely, the non-T lymphocyte population from peripheral blood responded poorly to SpA, and SpA did not stimulate non-T lymphocytes from tonsils. The addition of mitomycin-treated T lymphocytes from peripheral blood enhanced the response of blood non-T lymphocytes to protein A. This effect was not found when non-T lymphocytes isolated from tonsils were cultured with mitomycin-treated T lymphocytes. The proliferative response of unseparated cells or purified lymphocyte populations was enhanced when adherent cells were added to the cultures. It is concluded that the soluble form of protein A activates mainly T lymphocytes and does not induce B lymphocyte proliferation.
Assuntos
Ativação Linfocitária/efeitos dos fármacos , Proteína Estafilocócica A/farmacologia , Antígenos de Superfície/análise , Adesão Celular , Humanos , Linfócitos/classificação , Linfócitos/ultraestrutura , Mitógenos/farmacologia , Tonsila Palatina/citologia , Receptores de Droga/análise , Proteína Estafilocócica A/análiseRESUMO
Human polymorphonuclear neutrophils, monocytes, and lymphocytes were studied for their ability to synthesize Paf-acether when stimulated with the ionophore A 23187 (Io) or with specific secretagogues. When stimulated with Io, neutrophils produced 100 +/- 8.5 pmol Paf-acether 1 X 10(6) cells (mean +/- 1 SD, n = 5); monocytes were less efficient (44 +/- 3.3 pmol Paf-acether/1 X 10(6) cells), whereas lymphocytes were practically unable to form this mediator (1.0 +/- 0.4 pmol Paf-acether/1 X 10(6) cells). Neutrophils and monocytes released in the extracellular medium 49 and 37% of Paf-acether that they formed, respectively. We attempted to correlate the amount of Paf-acether produced by the various cell types with that of its precursors, 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine and 1-O-alkyl-sn-glycero-3-phosphocholine (2-lyso Paf-acether). In the three cell types, the amount of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine was sufficient to ensure the formation of 2-lyso Paf-acether and consequently that of Paf-acether. The quantity of 2-lyso Paf-acether formed appeared to be the limiting factor only in the case of the neutrophils. These cells increased their synthesis of Paf-acether in the presence of exogenous 2-lyso Paf-acether. To investigate the failure of lymphocytes to produce the mediator, the acetylating step of Paf-acether formation was studied, and we found a very weak activity (0.5 +/- 0.1 nmol Paf-acether/10 min/mg protein) in this cell type as opposed to monocytes (4.0 +/- 2.3 nmol Paf-acether/10 min/mg protein) and neutrophils (17.8 +/- 5.3 nmol Paf-acether/10 min/mg protein). These activities were doubled in Io-stimulated cells. Thus, the modulation of acetyl-transferase activity appears to be a key step in the regulation of Paf-acether biosynthesis. Also, the availability of 2-lyso Paf-acether could regulate Paf-acether synthesis in human neutrophils.
Assuntos
Acetiltransferases/sangue , Precursores Enzimáticos/sangue , Leucócitos/metabolismo , Fator de Ativação de Plaquetas/biossíntese , Precursores de Proteínas/sangue , Humanos , Leucócitos/enzimologia , Linfócitos/metabolismo , Monócitos/metabolismo , Neutrófilos/metabolismo , Fator de Ativação de Plaquetas/análogos & derivados , Fator de Ativação de Plaquetas/metabolismo , Fator de Ativação de Plaquetas/fisiologiaRESUMO
Cyclomunine, a cyclic peptide extracted from Fusarium equisiti, inhibits responses of human lymphocytes to mitogens, soluble antigens and allogeneic cells and the proliferation of lymphoblastoid cell lines. Cyclomunine has little effect on small lymphocytes but acts rather on lymphoblasts. It has no effect on fibroblasts and myeloid cells. Cyclomunine partially inhibits the generation of suppressor cells induced by Con A and the generation of cytotoxic T cells in a mixed lymphocyte culture and totally inhibits the in vitro synthesis of Ig by PBL. Cyclomunine merits consideration as a new in vitro anti-lymphoblastic agent.
Assuntos
Proteínas Fúngicas/farmacologia , Fusarium , Linfócitos/imunologia , Peptídeos Cíclicos/farmacologia , Membrana Celular/imunologia , Testes Imunológicos de Citotoxicidade , Humanos , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Mitógenos/farmacologia , Tuberculina/imunologiaRESUMO
The serum level of a circulating thymic factor (FTS) described in our laboratory diminishes in mice after adult thymectomy and with age. However, thymuses from old mice, when grafted into young adult thymectomized recipients lacking circulating FTS, can still partially restore the circulating FTS level of the recipients, whereas newborn thymuses are less efficient in restoring the serum level of FTS in old recipients than in young adult thymectomized recipients. Taken together, our results suggests that in addition to an intrinsic deficiency of the thymic secretion, "environmental" factors play a role in the disappearance of circulating FTS with age, the more so since we observed in old mouse sera factors inhibiting the in vitro biologic activity of FTS, factors that are absent from young mouse sera.
Assuntos
Envelhecimento , Timo/metabolismo , Animais , Animais Recém-Nascidos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Timectomia , Extratos do Timo/antagonistas & inibidores , Extratos do Timo/metabolismo , Timo/transplante , Transplante HomólogoRESUMO
We have studied the effects of a circulating thymic factor (TF), cyclic AMP (cAMP) and prostaglandins on T-lymphocyte differentiation in the mouse using three parameters: 1) 0-bearing cell percentage evaluated by a cytotoxicity test with anti-0 serum (A0S) plus complement; 2) 0-antigen presence on rosette forming cells (RFC) assessed by the inhibition of rosette formation with A0S; 3) lymphocyte mediated cytotoxicity (LMC) against allogeneic target cells after in vivo sensitization, using a chromium release assay.
Assuntos
AMP Cíclico/farmacologia , Linfócitos T/imunologia , Animais , Camundongos , Camundongos EndogâmicosRESUMO
The level of cyclic AMP (cAMP) in human lymphocytes in the presence or absence of isoproterenol stimulation was studied in various lymphocyte subpopulations containing different proportions of B and T lymphocytes. Lymphocytes from thymus and peripheral blood (which contain a majority of T cells) were more sensitive to isoproterenol action than lymphocytes from tonsils or adenoids (where B cells are predominant). Using purified B or T lymphocytes from peripheral blood, tonsils or adenoids, we observed an absence of B lymphocyte response to isoproterenol, whereas T lymphocytes, which had a lower basal c-AMP level than B cells, exhibited in all experiments a significant increase in cAMP content after isoproterenol stimulation. The intensity of the response varied in the different T lymphocyte subpopulations.