RESUMEN
Parathyroid adenoma is the most common cause of primary hyperthyroidism which leads to abnormal calcium homeostasis, hypercalcemia, and reduction in bone density. A 37-year-old female referred from a private health facility with a 1-year history of upper back swelling and pain. The pain was worse when sitting down for long periods and with movement and relieved by rest. There was no antecedent history of trauma, but the patient had noticed poor appetite and weight loss. There were no constipation, no abdominal discomfort, and no symptom suggestive of hyperthyroidism or hypothyroidism. General physical examination revealed kyphoscoliosis, and vital signs were within normal limits. Spine X-ray showed features of cervical spondylosis. Computed tomography (CT) scan and magnetic resonance imaging showed pathologic fractures of the right 9 thrib, anterior wedge compression, and reduction of T4 vertebrae with other abnormalities at T4-T5, T5-T6, T7-T8, T10-T11, and L4-L5 vertebrae. Bone marrow aspiration and serum electrophoresis were within normal limits. Serum calcium showed hypercalcemia. A CT scan of the neck was done which showed features of a right superior parathyroid adenoma. Blood count, other serum electrolytes, and thyroid function tests were all normal. A parathyroidectomy with right thyroid lobectomy was done. Histopathological examination of the resected parathyroid gland showed a diagnosis of parathyroid adenoma. A high index of suspicion is needed to diagnose this unusual presentation of parathyroid adenoma. Radiological imaging is an important tool for early diagnosis.
RESUMEN
Single-nucleotide polymorphisms (SNPs) can make an important contribution to our understanding of genetic backgrounds that may influence medical conditions and ethnic diversity. We undertook a systematic survey of genomic DNA for SNPs located not only in coding sequences but also in non-coding regions (e.g., introns and 5' flanking regions) of selected genes. Using DNA samples from 48 Japanese patients with rheumatoid arthritis (RA) as templates, we surveyed 41 genes that represent candidates for RA, screening a total of 104 kb of DNA (30 kb of coding sequences and 74 kb of non-coding DNA). Within this 104 kb of genomic sequences we identified 163 polymorphisms (1 per 638 bases on average), of which 142 were single-nucleotide substitutions and the remainder, insertions or deletions. Of the coding SNPs, 52% were non-synonymous substitutions, and non-conservative amino acid changes were observed in a quarter of those. Sixty-nine polymorphisms showed high frequencies for minor alleles (more than 15%) and 20 revealed low frequencies (<5%). Our results indicated a greater average distance between SNPs than others have reported, but this disparity may reflect the type of genes surveyed and/or the relative ethnic homogeneity of our test population.
Asunto(s)
Artritis Reumatoide/genética , Polimorfismo de Nucleótido Simple/genética , Alelos , Artritis Reumatoide/epidemiología , Frecuencia de los Genes , Humanos , Japón/epidemiología , Proteínas/genéticaRESUMEN
A 24-year-old woman had suffered from recurrent bacterial infections and clinical manifestations of systemic lupus erythematosus (SLE). Laboratory findings disclosed an elevated level of serum IgM, markedly decreased IgG, IgA, IgD and IgE levels, and low levels of serum complement. Both the CD40 and CD40 ligands appeared to be normally expressed. Assays of in vitro immunoglobulin production by lymphocytes showed that IgM was produced normally and that IgE but not IgG or IgA production was rescued by signaling through CD40 on B cells. The proliferative response of lymphocytes to phobol ester was markedly decreased, suggesting some impairment of signal transduction in the patient's lymphocytes.
Asunto(s)
Ligamiento Genético , Hipergammaglobulinemia/genética , Inmunoglobulina M/sangre , Síndromes de Inmunodeficiencia/genética , Lupus Eritematoso Sistémico/genética , Adulto , Antígenos CD40/análisis , Ligando de CD40 , Carcinógenos/farmacología , División Celular/efectos de los fármacos , División Celular/inmunología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Linfocitos/química , Linfocitos/citología , Linfocitos/efectos de los fármacos , Glicoproteínas de Membrana/análisis , Ésteres del Forbol/farmacología , Cromosoma XRESUMEN
In an X-linked immunodeficiency with hyper IgM (X-HIM), several mutations of genes coding for CD40 ligand are responsible for B-cell defects. However, it is controversial whether the defective class switching from IgM to IgG or IgA but not IgE is rescued by in vitro stimulations or not. In six X-HIM patients, signaling through CD40 induced IgE but not IgG or IgA secretion in vitro. When transferred into SCID mice, however, B-cells of X-HIM patients secreted as much IgG and IgA as those of healthy controls. Moreover, sIgG and sIgA expressions were also induced by the in vivo stimulation. These results support that B-cells of X-HIM patients are defective of in vitro class switching from IgM to IgG or IgA and show that the in vivo stimulations rescue the defective class switching and suggest that the class switching of IgE and that of IgG or IgA might be regulated quite differently.
Asunto(s)
Linfocitos B/inmunología , Hipergammaglobulinemia/patología , Inmunoglobulina A/genética , Inmunoglobulina G/genética , Inmunoglobulina M , Síndromes de Inmunodeficiencia/patología , Animales , Antígenos de Superficie/análisis , Linfocitos B/metabolismo , Humanos , Hipergammaglobulinemia/inmunología , Hipergammaglobulinemia/metabolismo , Cambio de Clase de Inmunoglobulina , Inmunoglobulina E/biosíntesis , Inmunoglobulina M/sangre , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Masculino , Ratones , Ratones SCIDRESUMEN
The integrin LFA-1 (CD11a/CD18) is a cell surface adhesion molecule required for leukocyte extravasation and subsequent immune and inflammatory responses. Rapid transition between nonadherent and adherent states of LFA-1 is of key importance to Ag-specific recognition of T lymphocytes. In this paper, LFA-1-mediated adhesiveness of peripheral blood (PB) and synovial fluid (SF) T lymphocytes to affinity-purified ICAM-1-coated plates was studied in patients with rheumatoid arthritis (RA) and in patients with non-RA panels, including osteoarthritis, ankylosing spondylitis, erythema nodosum, pseudogout, and pustulosis. LFA-1-mediated adhesiveness of SF T lymphocytes was not observed in any of the 10 non-RA patients studied, although cross-linking of the TCR on lymphocytes from these patients rapidly converted LFA-1 to an adhesive state. In contrast, SF T lymphocytes from 10 of 12 RA patients exhibited LFA-1-mediated adhesiveness without a requirement for cross-linking of the TCR. No difference was seen in the cell surface density of LFA-1 between non-RA and RA T lymphocytes, suggesting that the difference in adhesiveness was due to a high avidity state of LFA-1 on SF T lymphocytes in RA. Furthermore, exposure of PB T lymphocytes, which showed a low avidity state of LFA-1, to whole SF from RA patients that was depleted of T lymphocytes could induce a high avidity state of LFA-1 in vitro. Cellfree SF from RA patients also could stimulate adhesiveness, although to a lesser extent. These data suggest the existence of a LFA-1-activating environment that is selectively found in SF from RA patients.
Asunto(s)
Artritis Reumatoide/inmunología , Antígeno-1 Asociado a Función de Linfocito/análisis , Líquido Sinovial/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Antígenos de Diferenciación de Linfocitos T/metabolismo , Femenino , Humanos , Antígeno-1 Asociado a Función de Linfocito/metabolismo , Masculino , Persona de Mediana Edad , Unión Proteica , Linfocitos T/metabolismoRESUMEN
The ligand for CD40 (CD40L) is a membrane protein on activated T cells that induces B cell proliferation and differentiation. Several mutations of the CD40L gene were reported responsible for defective class switching of B cells in an X-linked immunodeficiency with hyper IgM (X-HIM). We studied four affected males from three families and found three independent mutations including new mutations of CD40L gene. In every X-HIM patient tested, however, anti-CD40 plus IL-10 did not induce class switching from IgM to IgG or IgA, even in the presence of Staphylococcus aureus Cowan I strain (SAC). CD4+ T cell clones, expressing CD40L on their surface, also did not rescue IgG or IgA induction by X-HIM peripheral blood B cells in vitro. But signaling through CD40 induced both B cell proliferation and IgE secretion when IL-4 was added to the culture. Taken together, these results show that in vitro signaling through CD40 rescues IgE but not IgG or IgA secretion by peripheral blood X-HIM B cells and suggest that in vivo CD40 and CD40L interaction might be necessary for IgG and IgA differentiation in X-HIM.
Asunto(s)
Antígenos CD/fisiología , Antígenos de Diferenciación de Linfocitos B/fisiología , Inmunoglobulina M/biosíntesis , Inmunoglobulinas/biosíntesis , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Cromosoma X , Secuencia de Aminoácidos , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Secuencia de Bases , Linfocitos T CD4-Positivos/inmunología , Antígenos CD40 , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina A/biosíntesis , Inmunoglobulina E/biosíntesis , Inmunoglobulina G/biosíntesis , Inmunoglobulina M/genética , Interleucina-1/farmacología , Interleucina-4/farmacología , Activación de Linfocitos , Masculino , Datos de Secuencia Molecular , Proteínas Recombinantes/farmacología , Valores de Referencia , Transducción de Señal , Linfocitos T/inmunologíaRESUMEN
Induction of Ig secretion in human tonsilar B cell by protein A-deficient Staphylococcus aureus WOOD 46 strain (SAW) was examined. SAW induced as much Ig secretion as protein A-rich S. aureus Cowan I strain (SAC) when IL-2 was present in the culture. Activated and resting B cells are separated by Percoll gradient to determine whether SAW stimulates either resting or activated B cells. In resting B cells, SAW plus IL-2 induced IgM secretion significantly, but neither IL-2 nor SAW alone induced IgM secretion. In activated B cells, however, IL-2 induced IgM secretion by itself and SAW plus IL-2 did not induce additional IgM secretion. These results suggest that SAW activates small resting B cells rather than preactivated B cells. Subsequently, mechanisms of B cell activation by SAW and SAC were compared. SAW did not induce [3H]-TdR incorporation through day 1 to 5, and the number of viable cells was not increased by SAW stimulation. Moreover, SAW did not induce significant tyrosine phosphorylation at any concentration tested, when tyrosine phosphorylation of B cells was examined. However, SAC induced both [3H]-TdR incorporation and tyrosine phosphorylation of B cell efficiently. In further experiments, induction of IL-2R and IgM mRNA expressions were examined. SAW by itself induced IL-2R and IgM mRNA expressions without affecting expression of membrane-type IgM mRNA. These results show that SAW activates human B cells in quite a different manner from SAC by up-regulating the expression of secretory type IgM mRNA without affecting cell proliferation nor tyrosine phosphorylation, proposing a distinct B cell activation model from SAC.
Asunto(s)
Linfocitos B/inmunología , ADN/biosíntesis , Activación de Linfocitos , Proteína Estafilocócica A/análisis , Tirosina/metabolismo , Células Cultivadas , Humanos , Inmunoglobulina M/genética , Inmunoglobulinas/biosíntesis , Fosforilación , ARN Mensajero/análisis , Receptores de Interleucina-2/análisis , Staphylococcus aureus/inmunologíaRESUMEN
Evidence of an acquired T cell-specific deficiency distinct from acquired immunodeficiency syndrome (AIDS) in a 63-yr-old Japanese female is provided. Recently, this patients suffered from primary invasive pulmonary aspergillosis. Skin tests to purified protein derivative of tuberculin (PPD) and Aspergillus antigens were negative. Upon admission to our hospital, her lymphocytes were exclusively unresponsive to T cell mitogens (concanavalin A, phytohemagglutinin, and OKT 3). The level of cells defined by monoclonal antibodies (CD1, CD2, CD3, CD4, WT31, and CD5) was less than 3%. In contrast, no decrease in the number of red blood cells, platelets, neutrophils or B cells was apparent. Five years ago, the patient had a normal white blood cell and lymphocyte count. However, over the following 4 yr, she developed lymphopenia. With medication, her pulmonary disease recovered, while lymphopenia still continued. The levels of immunoglobulins, complements and enzyme activities (adenosine deaminase and purine nucleoside phosphorylase) were normal. Moreover, several tests for HIV (ELISA and Western bolt) were negative suggesting that the T cell-specific deficiency was not a congenital immunodeficiency or AIDS but rather a new type of acquired immunodeficiency.
Asunto(s)
Síndromes de Inmunodeficiencia/etiología , Linfocitos T/inmunología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Aspergilosis/complicaciones , Femenino , Citometría de Flujo , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/inmunología , Técnicas In Vitro , Recuento de Leucocitos , Enfermedades Pulmonares Fúngicas/complicaciones , Activación de Linfocitos , Linfopenia/etiología , Linfopenia/inmunología , Persona de Mediana Edad , Infecciones Oportunistas/complicacionesRESUMEN
A 28-year-old woman with recurrent pneumonia was found to have selective IgG2, 4 subclass and IgE deficiencies. She had a history of repeated episodes of otitis media and sinusitis in childhood. Her total immunoglobulin level was slightly below the normal range, and selective deficiencies of IgG2, 4 and IgE were found. Although lymphocyte responses to several mitogens were within the normal ranges, peripheral blood mononuclear cells produced only IgM when stimulated by Staphylococcus aureus Cowan 1 and interleukin-2. Gene deletion of the IgG2, 4 subclass was not found, but polymorphism of the IgG gene was detected by DNA analysis of the patient's lymphocytes.
Asunto(s)
Disgammaglobulinemia/complicaciones , Deficiencia de IgG , Inmunoglobulina E/deficiencia , Neumonía/etiología , Adulto , Bronquiectasia/etiología , Disgammaglobulinemia/inmunología , Femenino , Humanos , RecurrenciaRESUMEN
Phytohemagglutinin (PHA) stimulated T cells from patients with systemic lupus erythematosus (SLE) showed hyporesponsiveness to interleukin 2 (IL-2) and expressed less p70/75 IL-2R than healthy controls. Ionomycine (IM, calcium ionophore) which selectively upregulated p70/75 expression, induced less p70/75 in patients with SLE than in healthy controls. However, intracellular calcium levels of T cells from patients with SLE increased as much as those from healthy controls, when T cells were stimulated by IM or PHA. Our results suggest that an impaired expression of p70/75 IL-2R in T cells from patients with SLE is not due to a defective calcium influx but to the events after the rise of calcium levels.
Asunto(s)
Calcio/metabolismo , Membranas Intracelulares/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Receptores de Interleucina-2/metabolismo , Linfocitos T/metabolismo , Adulto , División Celular/efectos de los fármacos , Femenino , Humanos , Interleucina-2/farmacología , Ionomicina/farmacología , Lupus Eritematoso Sistémico/patología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Fitohemaglutininas/farmacología , Linfocitos T/patologíaRESUMEN
There are two interleukin-2 receptor (IL-2R) subunits (p55 and p70/75) on human lymphocytes. Induction of the expressions of these IL-2R subunits was examined by the protein kinase-C (PK-C) activator (phorbol myristate acetate, PMA) and the calcium ionophore, ionomycine (IM). IM induced predominantly p70/75 expression on human T and B cells as indicated by the results of chemical crosslinking studies and binding assays. In contrast, PMA induced p55 expression significantly. These results suggest that the calcium-calmodulin and PK-C pathways regulate p70/75 and p55 expressions differently, and indicate that these intracellular signal messengers could control the responsiveness to IL-2, changing the affinity and number of receptors in vivo.
Asunto(s)
Linfocitos B/inmunología , Receptores de Interleucina-2/biosíntesis , Linfocitos T/inmunología , Linfocitos B/efectos de los fármacos , Línea Celular , Células Cultivadas , Humanos , Ionomicina/farmacología , Cinética , Sustancias Macromoleculares , Peso Molecular , Tonsila Palatina/inmunología , Receptores de Interleucina-2/aislamiento & purificación , Receptores de Interleucina-2/metabolismo , Linfocitos T/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
A patient with ataxia telangiectasia was treated with recombinant interleukin-2 (rIL-2) and the resulting immunological effects evaluated. The patient lacked IL-2 production, and immunoglobulin synthesis was also impaired. Treatment with IL-2 selectively increased serum IgM without any significant side effects. Therapy also restored B-cell function in vitro. IgM production as well as the proliferative response to Staphylococcus aureus strain Cowan I. These results suggest that IL-2 treatment may correct both T-cell and B-cell defects.
Asunto(s)
Ataxia Telangiectasia/tratamiento farmacológico , Inmunoglobulina M/análisis , Interleucina-2/uso terapéutico , Adolescente , Ataxia Telangiectasia/inmunología , Humanos , Interleucina-2/inmunología , MasculinoRESUMEN
Using radiolabeled interleukin-2 (IL-2), affinity cross-linking and binding assays revealed that the expression of intermediate-affinity IL-2 binding molecules (p70/75) on freshly prepared T cells from patients with systemic lupus erythematosus (SLE) was significantly decreased in comparison with that in normal subjects. The proliferative response of T cells to high doses of IL-2 was also reduced in patients with SLE. The decreased expression of p70/75 reflects the hyporesponsiveness to IL-2 of T cells in patients with SLE.
Asunto(s)
Lupus Eritematoso Sistémico/metabolismo , Receptores de Interleucina-2/metabolismo , Linfocitos T/metabolismo , Adulto , División Celular/efectos de los fármacos , Femenino , Humanos , Interleucina-2/farmacología , Masculino , Persona de Mediana Edad , Ensayo de Unión Radioligante , Linfocitos T/efectos de los fármacos , Linfocitos T/patologíaRESUMEN
The age-associated changes of the expression of IL-2 binding molecules p55/Tac(alpha chain) and p70/75(beta chain) were examined after phytohemagglutinin (PHA) stimulation. The expressions of both p55/Tac molecules and p70/75 molecules were significantly reduced in the aged compared with those in the young persons. The amounts of p55/Tac and p70/75 molecules on T cells from the aged were 55% and 59% of those on young ones, respectively. The ratio of the amount of p70/75 to that of p55/Tac in aged T cells was 0.28 and that in young ones was 0.26. The ratio was somewhat higher in the aged but not significantly. We also examined the kinetics of IL-2 internalization mediated by its receptor. The calculated t1/2 of receptor-mediated IL-2 internalization was 17 min in the aged and 16 min in the young, respectively. There was no kinetic difference between the 2 groups. The percentage of the internalized IL-2 to the sum total was 58.2% in the aged and 73.4% in the young (P less than 0.02). the amount of internalized IL-2 in T cells from the aged was 48.6% of that from the young (P less than 0.01).
Asunto(s)
Envejecimiento/metabolismo , Interleucina-2/metabolismo , Receptores de Interleucina-2/metabolismo , Linfocitos T/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Electroforesis en Gel de Poliacrilamida , Humanos , Técnicas In Vitro , Cinética , Activación de Linfocitos , Fragmentos de Péptidos/metabolismo , Fitohemaglutininas/farmacologíaRESUMEN
Expressions and functional roles of novel IL-2 binding molecules (p70, 75) in the differentiation of B cells into Ig secreting cells were explored by using human several B cell lines and tonsillar B cells. Affinity-crosslinking studies revealed that five of nine B cell lines expressed p70 and p75 without detectable Tac antigen (p55) expression and the expression was associated with B cell maturation. In tonsillar B cells, small high-density B cells did not express p70 and p75, whereas large low-density B cells, which were thought to be activated in vivo, expressed them. Binding assays of radiolabeled IL-2 showed that the affinity of these molecules was intermediate (kD = 1-3 nM, 700-3,000 sites/cell). Furthermore, high concentrations of IL-2 (greater than 100 U/ml) induced Ig productions in large B cells and two of five cell lines. These results taken together suggest that B cells may express novel IL-2 binding molecules, associated with B cell differentiation and differentiate into Ig secreting cells by IL-2 through novel IL-2 binding molecules.
Asunto(s)
Linfocitos B/metabolismo , Interleucina-2/metabolismo , Receptores Inmunológicos/aislamiento & purificación , Antígenos de Superficie/biosíntesis , Linfocitos B/citología , Linfocitos B/inmunología , Diferenciación Celular , Línea Celular , Relación Dosis-Respuesta Inmunológica , Humanos , Inmunoglobulinas/biosíntesis , Interleucina-2/fisiología , Cinética , Activación de Linfocitos , Peso Molecular , Receptores Inmunológicos/fisiología , Receptores de Interleucina-2 , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis TumoralRESUMEN
Novel IL-2-binding molecules (p70 and p75) mediating internalization and degradation of IL-2 were examined by employing a human B lymphoblastoid line, SKW6-4 cells. High concentrations of IL-2 induced IgM secretion in these cells through a receptor distinct from Tac antigen. The acid-wash technique revealed that more than 60% of 125I-labeled IL-2 bound to the cells became acid-unremovable in the first 30 min of incubation at 37 degrees C and degradation products of 125I-IL-2 increased after 30 min of incubation. Treatment of the cells with NaN3 buffer inhibited the appearance of acid-unremovable 125I-IL-2, suggesting that acid-unremovable 125I-IL-2 was not due to fluid-phase pinocytosis but due to internalization. Loss of labeled bands by incubation of cells with 125I-IL-2 at 37 degrees C before affinity cross-linking demonstrated that 125I-IL-2 was internalized via novel IL-2-binding molecules. These results suggest that novel IL-2-binding molecules are responsible for internalization and may mediate signal transduction in B cells in the absence of Tac antigen.
Asunto(s)
Linfocitos B/metabolismo , Interleucina-2/metabolismo , Receptores Inmunológicos/fisiología , Azidas/farmacología , Linfocitos B/fisiología , Línea Celular , Reactivos de Enlaces Cruzados , Humanos , Inmunoglobulina M/biosíntesis , Interleucina-2/farmacología , Pinocitosis , Receptores Inmunológicos/aislamiento & purificación , Receptores de Interleucina-2 , Azida SódicaRESUMEN
Expression of p70/75 IL-2-binding molecules and their functional roles in induction of Ig secretion by IL-2 were examined in human B cells. IL-2, at high concentrations induced higher levels of Ig secretion in Staphylococcus aureus strain Cowan I (SAC)-activated B cells than at low concentrations. About 50% of SAC-activated B cells, lacking Tac antigen, were also responsive to Ig secretion by IL-2, although the required dose of IL-2 was higher than that for Tac-positive B cells. H-31 antibody which recognizes Tac antigen did not inhibit the induction of Ig secretion by high concentrations of IL-2 in both Tac-negative and Tac-positive B cells, suggesting that IL-2 might induce Ig secretion through a receptor distinct from Tac antigens. In contrast, IL-2 was ineffective in the absence of SAC stimulation even at high concentrations. Upon analysis by SDS-PAGE, p70/75 IL-2-binding molecules were detected on Tac-negative SAC-activated B cells. Similar IL-2-binding molecules distinct from Tac antigen (p55) were detected in both Tac-positive B and T cells. However, neither p55 nor p70/75 IL-2-binding molecules could be detected in the absence of SAC stimulation. These observations suggest that p70/75 IL-2 binding molecules are induced in human B-cells in the presence or absence of Tac antigen by SAC stimulation and these determinants play an important function in the transduction of IL-2 associated signal for B cell differentiation.
Asunto(s)
Linfocitos B/metabolismo , Interleucina-2/metabolismo , Receptores Inmunológicos/análisis , Anticuerpos Monoclonales/farmacología , Antígenos de Superficie/análisis , Antígenos de Superficie/inmunología , Linfocitos B/clasificación , Unión Competitiva , Electroforesis en Gel de Poliacrilamida , Citometría de Flujo , Humanos , Inmunoglobulinas/biosíntesis , Interleucina-2/farmacología , Activación de Linfocitos , Fenotipo , Receptores Inmunológicos/fisiología , Receptores de Interleucina-2 , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis TumoralRESUMEN
Cellular and genetic analyses of interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression were examined in a immunodeficient patient and his family members. Mononuclear cells (MNC) of the patient showed no proliferative response (stimulation index, less than 2) to T-cell mitogens (PHA and Con A) and were defective in IL-2 production and IL-2R expression (less than 1%), whereas productions of other lymphokines (B-cell differentiation factor and IFN-gamma) were not impaired significantly. His brother died of the same disease and his father also lacked in proliferative response and IL-2 production by PHA stimulation. In Southern blot analyses using DNA probes of IL-2 and IL-2R, patterns of the patient were the same as those of healthy volunteers, whereas the transcription of DNA coding for IL-2R to mRNA was lacking in the patient. These results suggest that inheritant defects of IL-2 production and IL-2R expression reside in this family and the defects are not linked to DNAs coding for IL-2 and IL-2R but to a transcriptional deficiency.
Asunto(s)
Síndromes de Inmunodeficiencia/metabolismo , Interleucina-2/biosíntesis , Receptores Inmunológicos/biosíntesis , Linfocitos T , Concanavalina A/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Síndromes de Inmunodeficiencia/genética , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/efectos de los fármacos , Linfocinas/biosíntesis , Masculino , Fitohemaglutininas/farmacología , Receptores Inmunológicos/deficiencia , Receptores de Interleucina-2RESUMEN
In this report, we examined whether novel interleukin 2 (IL-2) binding molecules (p70/75) are responsible for signal transduction and internalization of IL-2 in T cells by using a monoclonal antibody H-31 to Tac antigens. We found that H-31 inhibited the binding of IL-2 to Tac antigens but not novel IL-2 binding molecules. Scatchard plot analysis revealed that in the presence of H-31, intermediate affinity sites (Kd = 1 to 1.5 nM) were detectable and the number of them was similar to that of high affinity IL-2 receptor (IL-2R) (Kd = 10 to 15 pM) in the absence of H-31. Furthermore, the kinetics of endocytosis of IL-2 via p70/75 showed the same pattern as via high affinity IL-2R. Finally, high doses of IL-2 (100 to 10,000 U/ml) are required for the proliferation of T cells in the presence of H-31, whereas in the absence of H-31, physiologic doses of IL-2 (1 to 100 U/ml) induced the proliferation. These results taken together suggest that novel IL-2 binding molecules are related to signal transduction of IL-2 and that Tac antigens are essential for constructing of high affinity IL-2R, although Tac antigens may not be responsible for signal transduction.