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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A general procedure is described for the production of human monoclonal antibodies from peripheral blood lymphocytes immunized in vitro against T-cell-dependent antigens. These lymphocytes immunized in culture were used to produce human-human or human-mouse hybridomas secreting monoclonal antibodies specific for digoxin, hemocyanin, a recombinant fragment of the gp120 envelope glycoprotein of human immunodeficiency virus (PB1), or a melanoma-associated antigen (p97). Depletion of a lysosome-rich cell population, containing large granular lymphocytes, monocytes, cytotoxic T cells, and a subset of CD8-positive T cells, was shown to be crucial before the cells could be immunized in vitro. This depletion was accomplished by treating the peripheral blood lymphocytes with the lysosomotropic agent L-leucine methyl ester. In addition, the in vitro immunization had to be supported by interleukin 2, gamma-interferon, and B-cell growth and differentiation factors, derived from irradiated, pokeweed-mitogen-stimulated human T cells. The production of human monoclonal antibodies from primary, antigen-specifically activated peripheral lymphocytes might obviate the need to immunize volunteers or patients.
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PMID:Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. 313 70

We have selected 11 patients with primary immunodeficiency disorders predominantly affecting T lymphocyte function (four with ataxia-telangiectasia (AT), four with common variable immunodeficiency (CVI) and one each with Wiskott-Aldrich syndrome, hyper-IgE syndrome and combined immunodeficiency) with defective gamma interferon (IFN-gamma) production in vitro. Induction with phytohaemagglutinin showed low interleukin 2 (IL-2) production concomitant with reduced IFN-gamma titres. However the addition of 10 U/ml of rIL-2 to cultures stimulated with staphylococcal enterotoxin B or galactose oxidase failed to restore IFN-gamma production in defective cases. IFN-gamma was titrated by both bioassay and immunoradiometric assay, ruling out the possible release of inactive or altered IFN-gamma molecules. Normal levels of IFN-gamma were found in patients of patients with AT, as well as in two AT and two CVI cases, demonstrating heterogeneity of defects within these syndromes. Soluble inhibitors or cellular suppression of IFN-gamma were not observed in mixing experiments. The possibility that defective interaction between accessory cells and T lymphocytes might account for the poor response to the inducing agents was ruled out as no IFN-gamma was produced using a calcium ionophore--which bypasses this step--in seven patients with absolute IFN-gamma deficiency.
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PMID:Evidence that defective gamma interferon production in patients with primary immunodeficiencies is due to intrinsic incompetence of lymphocytes. 313 28

In AIDS elevated serum Ig levels and autoimmune phenomena indicate that B cells are also involved. The human immunodeficiency virus (HIV) can be cultivated in B cells, and HIV can stimulate B cells. In order to characterize the B-cell dysfunction and conditions for modulating it, functional studies with highly purified B cells were done in four patients with PGL and HIV-positive sera. Data were compared with those from patients with AIDS and normal controls. The experiments consisted of an in vitro study of the differentiation response (IgM/G secretion into culture supernatants) to a T cell-independent polyclonal B-cell activator (PBA) [Klebsiella pneumoniae, KlebsM]. A weak increase in IgM/G levels under stimulatory conditions was characteristic. Addition of recombinant interleukin 2 (rIL2) failed to increase the spontaneous Ig levels. However, coculture experiments using KlebsM and rIL2 resulted in Ig levels like those known from healthy individuals. Patients with frank AIDS did not respond with increased IgG secretion. This indicates that the abnormal B-cell differentiation response to PBAs can be modulated by rIL2 in patients with PGL and partly in AIDS (only IgM).
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PMID:The in vitro influence of rIL2 on the B-cell dysfunction in patients with persistent generalized lymph node enlargement (PGL) or AIDS. 326 95

The posttrauma immunodeficiency syndrome and the related postsurgery immunodeficiency syndrome are essential for the infections often occurring after polytrauma and major surgery. Data are given here showing that after such events the levels of immunoglobulins; the complement factors C3C, C4 and C Factor B; and the numbers of circulating lymphocytes and of the subpopulations CD3, CD4, CD8 and natural killer cells as well as the stimulatory capacity of mononuclear cells to mitogen fall; while the levels of acute phase proteins, neopterin and interleukin 2 receptors and the spontaneous uptake of thymidine by mononuclear cells become augmented. Extent and duration of these changes and the rate of subsequent infections depend on the extent and kind of surgery (minor, major, clean, contaminated). However, crucial factors of the posttrauma and postsurgery immunodeficiency syndromes are not yet elucidated and relevant predictive parameters for infections are not at hand. These are essential prerequisites to initiate future immunomodulatory measures which should be added to the use of intravenous immunoglobulins yielding so far distinct but limited benefits for the prevention of infections after polytrauma and major surgery.
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PMID:Immunodeficiency after major trauma and selective surgery. 339 84

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution resulted in a conditioned aversion to saccharin and a conditioned suppression of natural killer cell (NKC) cytotoxicity. In this study, male Sprague-Dawley rats were conditioned by pairing saccharin with 50 mg/kg CY, an immunosuppressive drug with noxious gastrointestinal side-effects. Twenty-two and 26 days later, re-exposure of conditioned animals to saccharin alone re-enlisted the immunosuppressive effects of CY when NKC cytotoxicity was measured on day 29. Although CY also suppressed spleen cell number, IgG antibody titers and interleukin 2 (IL2) production, these immune responses did not appear to be affected by the behavioral conditioning paradigm in this experiment. Unique aspects of this study include the ability to measure multiple immune responses in a single rat and the finding that previous reports of behaviorally conditioned immunosuppression can be extended to another parameter, NKC cytotoxicity. These findings could have significant implications to human medicine, especially in the area of autoimmunity and immunodeficiency, and intervention and treatment of cancer.
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PMID:Cyclophosphamide-conditioned suppression of the natural killer cell response in rats. 349 Jun 76

The antigen receptor expressed on most T lymphocytes is a disulphide-linked heterodimer (Ti) that is composed of alpha-chain and beta-chain subunits. On the surface of human T lymphocytes, Ti is non-covalently associated with three invariant proteins, designated CD3-gamma, -delta, and -epsilon. It has been suggested that Ti is obligatory for CD3 expression. But a T leukaemia cell line, IL-2 (interleukin 2) dependent T-cell clones established from fetal blood and IL-2 dependent cell lines established from immunodeficiency patients with bare lymphocyte syndrome and ectodermal dysplasia syndrome have recently been shown to express CD3, but not Ti (detected due to monoclonal antibody WT31). These lymphocytes may express the product of the T-cell antigen receptor gamma (TCR-gamma) gene, rather than the alpha/beta heterodimer, in association with CD3. Preliminary studies suggested that T cells expressing CD3 but lacking Ti are present in low frequency in normal lymphoid tissues. Here we show that in normal blood and thymus CD3+, WT31-T cells express neither CD4 nor CD8. The low frequency (less than 0.2-0.9% of total thymocytes) of CD3+, WT31- cells in the thymus suggests that this population does not represent a major stage of thymic development and may be a distinct lineage of T cells.
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PMID:Presence of Ti (WT31) negative T lymphocytes in normal blood and thymus. 349 23

Experimental and clinical systems have been developed to analyze both the in vitro and in vivo effects of highly purified interleukin 2 (IL2) as a potential therapeutic adjunct for neoplasia, immunodeficiency and infectious disease. Animal models, clinical in vitro studies, as well as preliminary clinical trials of IL2 in vivo show that this lymphokine may provide a necessary signal for the activation of thymus-derived T cells in immunologically-compromised hosts.
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PMID:Potential use of human interleukin 2 as an adjunct for the therapy of neoplasia, immunodeficiency and infectious disease. 388 67

The development of a competent immunoregulatory response in the face of an antigenic challenge is modulated by soluble proteins of relatively low molecular mass. Lymphokines and monokines, secreted by cells of T lineage and cells of the monocyte/microphage series, respectively, function in a bimodal amplification network that results in the proliferation and differentiation of the immunoregulatory cells. Interleukin 1 is typically assayed by its effect on thymocytes or by its ability to promote the T cell-dependent release of interleukin 2. Interleukin 2 is routinely measured by its ability to support the long-term growth of cultured T cells, whereas B cell growth factor is measured by its ability to support the long-term growth of cultured B lymphocytes. The availability of homogeneous purified factors and the subsequent availability of monoclonal antibodies against these reagents should allow for the development of rapid quantitative assays for these analytes in diverse biological fluids. In addition, large quantities of purified reagents will promote studies to determine therapeutic efficacy in several immunodeficiency syndromes.
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PMID:Lymphokines and monokines as regulators of human lymphoproliferation. 643 65

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies OKT3 and Pan T2, to induce proliferation and interleukin 2 (IL2) production in peripheral blood lymphocytes (PBL) from 21 homosexual patients: 12 with Kaposi's sarcoma (KS), 4 with reactive lymphadenopathy, and 5 with opportunistic infections. All patients with KS and opportunistic infections had significantly lower mitogen-stimulated DNA synthesis, as compared to the controls, irrespective of the mitogen used (P less than 0.01). The patients with lymphadenopathy exhibited significantly lower responses only in the OKT3 assay as compared to normals (P = 0.009). The production of endogenous IL2 was significantly lower in PBL cultures from patients with KS and with opportunistic infections, irrespective of the mitogen used, as compared to healthy male controls, and also significantly lower in the Pan T2-stimulated cultures from patients with lymphadenopathy. The addition of highly purified IL2 was able to restore partially lymphocyte proliferation in vitro in the presence of these mitogens in all patients. Our studies demonstrate (1) that male homosexuals even without clinical manifestations of immunodeficiency frequently exhibit a proliferative T-cell defect when anti-T-cell monoclonal antibodies rather than PHA are used as mitogens, (2) that this proliferative defect is associated with defective IL2 production, and (3) that this defect is at least in part correctable in vitro by highly purified IL2.
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PMID:Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2. 660 43

Studies were designed to investigate whether the cellular immunodeficiency state observed in human glioblastoma patients could be due to inhibitory factors released by the tumor cells. Cultured human glioblastoma cells were found to secrete an interleukin 1-like factor (m.w. 22,000) and a factor (m.w. 97,000) that inhibits interleukin 2 (IL 2)-dependent T cell mechanisms. This is demonstrated by its inhibitory effect on the IL 2-induced proliferation of T cell clones and on the induction of alloreactive cytotoxic T cells in mixed lymphocyte cultures. Additionally the glioblastoma cell-derived 97,000-m.w. factor inhibited growth of neuroblasts but not of fibroblasts and thus shares the characteristics of the neuroblast growth inhibition factor (NGIF) previously detected in the supernatant of fetal rat glia cell cultures. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.
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PMID:Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects. 660 49


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