Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatibility antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.     

Cytotoxic antibody in normal human serums reactive with tumor cells from acute lymphocytic leukemia

Serums showing complement-dependent cytotoxic reactions to acute lymphocytic leukemia cells were detected in three normal unimmunized subjects. These serums were reactive with tumor cells from 514 (514 tested) acute lymphocytic leukemia patients, and three (12 tested) patients with acute myelocytic leukemia; they did not react with tumor cells from patients with acute monocytic leukemia (two tested), with chronic lymphocytic leukemia (two tested) or with leukolymphosarcoma (two tested); nor did they react with normal lymphocytes from 52 different donors. These reactive serums appear to recognize antigens primarily associated with acute lymphocytic leukemia.     

Detection of an antigen associated with acute leukemia

Antiserums to a purified cell membrane component from a Burkitt's lymphoma tissue culture cell line were produced in rabbits. These antiserums were cytotoxic to peripheral white blood cells from 8 of 15 patients with acute leukemia and 5 of 41 relatives, but not to peripheral white blood cells from leukemia patients in clinical remission or from normal individuals. These antiserums appear to be detecting an acute leukemia associated antigen or antigens.     

Antigens specific for human lymphocytic and myeloid leukemia cells: detection by nonhuman primate antiserums

Primate antiserums to human leukemia cells can detect antigens specific for lymphocytic leukemia cells or antigens present on certain myeloid leukemia cells. The antigen specific for lymphocytic leukemia cells is destroyed by treatment with neuraminidase or trypsin. Tryptic digests of lymphocytic leukemia cells contain the antigen, which has a high molecular weight.     

A virus-encoded "superantigen" in a retrovirus-induced immunodeficiency syndrome of mice.

The development of an immunodeficiency syndrome of mice caused by a replication-defective murine leukemia virus (MuLV) is paradoxically associated with a rapid activation and proliferation of CD4+ T cells that are dependent on the presence of B cells. The responses of normal spleen cells to B cell lines that express the defective virus indicated that these lines express a cell surface determinant that shares "superantigenic" properties with some microbial antigens and Mls-like self antigens. This antigen elicited a potent proliferative response that was dependent on the presence of CD4+ T cells and was associated with selective expansion of cells bearing V beta 5. This response was markedly inhibited by a monoclonal antibody specific for the MuLV gag-encoded p30 antigen.     

Leukemia-associated antigens in the mixed leukocyte culture test

Patients with acute leukemia (blast cells in the peripheral blood) manifest antigens in the one-way mixed leukocyte culture test. Leukocytes from normal patients and leukocytes of patients in remission do not clearly show these antigens. These antigens could be leukemia-associated antigens in man.     

Autologous immune-complex pathogenesis of experimental allergic glomerulonephritis

A renal tubular epithelial antigen is deposited in association with gamma globulin and complement in glomeruli from rats with experimental allergic glomerulonephritis induced by immunization with renal tubular antigens. Apparently, in normal kidneys this antigen is concentrated in the distal segment of the proximal convoluted tubular epithelium, and the principal source of this antigen in the glomerular deposits is autologous. This form of glomerulonephritis provides an experimental prototype for what may be termed "autologous immunecomplex" diseases.     

T and Tn, general carcinoma autoantigens

Primary and metastatic carcinomas are epithelial in origin and comprise by far the largest group of malignant tumors in humans. In most of these tumors, T and Tn antigens, whose epitopes have been synthesized, are uncovered and immunoreactive. In all other tissues T and Tn antigens are masked and not accessible to the immune system; they are generally precursors in normal complex carbohydrate chains. Thus, carcinomas have antigens recognized as foreign by the patients' immune system. The expression of T and Tn antigens has pathogenic and clinical consequences, and the antigens themselves are powerful histological markers in carcinoma diagnosis and frequently in prognosis. Most patients distinguish their carcinoma from all other cells, as shown by strong autoimmune responses to T antigen. These responses are readily measured by assays, and they allow detection of carcinomas with greater sensitivity and specificity frequently earlier than previously possible. Moreover, the extent of T and Tn expression often correlates with carcinoma differentiation; on a molecular level, clustered T- and Tn-active structures on carcinoma cell surfaces may be involved in invasion.     

Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate

Antigen-presenting cells (APCs) internalize antigens and present antigen-derived peptides to T cells. Although APCs have been thought to exhibit a well-developed capacity for lysosomal proteolysis, here we found that they can exhibit two distinct strategies upon antigen encounter. Whereas macrophages contained high levels of lysosomal proteases and rapidly degraded internalized proteins, dendritic cells (DCs) and B lymphocytes were protease-poor, resulting in a limited capacity for lysosomal degradation. Consistent with these findings, DCs in vivo degraded internalized antigens slowly and thus retained antigen in lymphoid organs for extended periods. Limited lysosomal proteolysis also favored antigen presentation. These results help explain why DCs are able to efficiently accumulate, process, and disseminate antigens and microbes systemically for purposes of tolerance and immunity.     

Immortalization of human T lymphocytes after transfection of Epstein-Barr virus DNA

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, has the ability to transform human B lymphocytes. No other cell type has been experimentally transformed by EBV, either by intact virions or naked viral DNA and subgenomic fragments. Two immortalized human T-lymphoblastoid cell lines have now been established by transfecting cord blood lymphocytes with purified B95-8 viral DNA enclosed in fusogenic Sendai virus envelopes (RSVE) and then exposing the cells to EBV from a P3HR-1 cell subclone. One of these lines, which has been fully characterized, is termed HBD-1. This line is positive for EBV DNA and expresses surface OKT11, OKT4, and Tac receptors, but not M-1, mu immunoglobulin chains, EBV receptors, or B-1 surface markers. The cells contain fully rearranged T-cell receptor genes and germline immunoglobulin genes. The karyotype of the cells is normal, they do not require interleukin-2 for growth, and do not contain human T-lymphotropic virus type I. However, the HBD-1 cells contain incomplete EBV genomes and express several EBV-determined antigens, including the early antigen type D, membrane antigens, but not EBV-determined nuclear antigen (EBNA). This association of the EBV genome with permanently growing hematopoietic cells of non B-cell lineage should prove useful in studies on the mechanism of EBV-mediated cell transformation.     

Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells

T-cell receptors bind antigens only when the antigens are exposed on the cell surface. This can be studied best in the interaction of cytolytic T lymphocytes (CTL) with target cells because the recognition and binding event can be separated from the lytic phase. Studies with CTL clones specific for HLA-A2 and HLA-B7 demonstrated that conjugates of CTL's and target cells can be formed in the absence of specific antigen recognition. Furthermore, T-cell receptor and target antigen cannot interact unless there is conjugate formation. This indicates that nonspecific conjugate formation between CTL's and target cells precedes the recognition of specific antigen by the T-cell receptor.     

Serological identification of an Ir-region product

Reciprocal immunization of congenic lines differing in the middle portion of the H-2 complex leads to the production of antibodies which react with an antigen or antigens controlled by the Ir region. The antigen designated Ir-1.1 seems to be present only on a subpopulation of lymphocytes from lymph nodes and spleen. It is absent on bone marrow cells.     

Autoimmune encephalomyelitis: activation of thymus lymphocytes against syngeneic brain antigens in vitro

Thymus lymphocytes of normal adult rats were autosensitized in vitro against soluble antigens extracted from the brains of syngeneic rats. Injection of the autosensitized lymphocytes into syngeneic rats led to the development of brain lesions suggestive of autoimmune encephalomyelitis. Injection of control lymphocytes or the antigen extract alone did not cause lesions. Since sensitization in vitro requires the presence of lymphocytes programmed with specific receptors, the results indicate that normal rats have lymphocytes capable of recognizing central nervous system self-antigens. Hence, regulatory mechanisms, inoperative in vitro, probably function in vivo to prevent immune activation of self-recognizing lymphocytes and autoimmunity. This concept suggests a new approach to exploring the pathogenesis of autoimmune diseases.     

HTLV-V: a new human retrovirus isolated in a Tac-negative T cell lymphoma/leukemia

A new human retrovirus was isolated from a continuous cell line derived from a patient with CD4+ Tac- cutaneous T cell lymphoma/leukemia. This virus is related to but distinct from human T cell leukemia/lymphoma virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus (HIV-1). With the use of a fragment of provirus cloned from one patient with T cell leukemia, closely related sequences were found in DNA of the cell line and of tumor cells from seven other patients with the same disease; these sequences were only distantly related to HTLV-I. The phenotype of the cells and the clinical course of the disease were clearly distinguishable from leukemia associated with HTLV-I. All patients and the wife of one patient showed a weak serological cross-reactivity with both HTLV-I and HIV-1 antigens. None of the patients proved to be at any apparent risk for HIV-1 infection. The name proposed for this virus is HTLV-V, and the date indicate that it may be a primary etiological factor in the major group of cutaneous T cell lymphomas/leukemias, including the sporadic lymphomas known as mycoses fungoides.     

Autologous red cell agglutination assay for HIV-1 antibodies: simplified test with whole blood

An antibody detection procedure based on agglutination of autologous red cells has been developed for samples of whole blood. A nonagglutinating monoclonal antibody to human red blood cells conjugated to a synthetic peptide antigen (in this case residues 579 to 601 of the HIV-1 envelope precursor, Arg-Ile-Leu-Ala-Val-Glu-Arg-Tyr-Leu-Lys-Asp-Gln-Gln-Leu-Leu-Gly-Ile-Trp- Gly-Cys - Ser-Gly-Lys) permitted the detection of antibodies to the human immunodeficiency virus type 1 (HIV-1) in 10 microliters of whole blood within 2 minutes. Agglutination was specifically inhibited by addition of synthetic peptide antigen but not by unrelated peptides. The frequency of false positive results was 0.1% with HIV-1 seronegative blood donors (n = 874). The false negative results were approximately 1% (n = 81). The autologous red cell agglutination test is potentially suitable for simple, rapid, qualitative screening for antibodies to a variety of antigens of medical and veterinary diagnostic significance.     

Mitosis: induction by cultures of human peripheral lymphocytes

Ribosomal RNA extracted from peripheral lymphocytes, which had been recently stimulated by specific antigens to which the donor was sensitized, is capable of promoting transformation and mitosis when added to cultures of autologous unstimulated lymphocytes.     

Antireceptor antiserum causes specific inhibition of reactivity to rat histocompatibility antigens

The antigen receptor of lymphocytes destined to form antibody appears to have the characteristics of the immunoglobulin produced. Antibody directed against the combining region of this immunoglobulin should interact with the combining region of the cell receptor for the antigen. Purified Lewis rat alloantibody prepared against Brown Norway (BN) rat histocompatibility antigens was used to immunize L x BN F(1) hybrids. The resultant antiserum has anti-receptor activity because (i) it yields precipitin lines in gel diffusion when reacted against the immunizing alloantibody; (ii) it inhibits the hemagglutinin antibody response of Lewis rats to BN histocompatibility antigens; and (iii) it inhibits the local graft-versus-host response of Lewis lymphoid cells against BN antigens. This suggests that antireceptor antibody may inhibit cell-mediated responses as well as antibody responses to histocompatibility antigens and may play a role in the regulation of immune responses to such antigens.     

流式细胞仪检测CD55与CD59诊断阵发性睡眠性血红蛋白尿症

目的 :探讨 CD55、CD59对阵发性睡眠性血红蛋白尿症 (PNH)的临床诊断意义。方法 :应用流式细胞仪 (FCM)检测人体外周血红细胞、粒细胞、淋巴细胞的表面抗原 CD55、CD59的表达水平。结果 :PNH患者 CD55、CD59表面抗原在红细胞、粒细胞、淋巴细胞上均有不同程度的缺乏 ,尤以红细胞、粒细胞较明显。再生障碍性贫血患者的红细胞、粒细胞、淋巴细胞 CD55、CD59表面抗原标记阳性率与正常对照组比较差异无显著性 (P>0 .0 5)。结论 :流式细胞仪检测 PNH患者外周血红细胞、粒细胞、淋巴细胞 CD55、CD59表面抗原具有重要的临床诊断意义。     

Immune specific induction of interferon production in cultures of human blood lymphocytes

Human blood lymphocytes stimulated with nonviral antigens in vitro produce an antiviral substance with the biological and biochemical characteristics of interferon. The induced response was specific for cells obtained from immune donors. Cells from nonimmune donors did not produce interferon on exposure to these substances. The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased. Interferon production was maximum during days 4 to 7 in culture. In contrast, phytohemagglutinin-induced interferon was primarily produced during the first 4 days in culture.