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Biomedical subjects

H C Lane

Publications and source records attributed to H C Lane.

At least 199 records · Page 11Linked to original sources
PubMed1983

Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Development of a human T-T cell hybridoma secreting B cell growth factor.

The success of long-term culture of normal human and murine B cells has been hampered by the limited availability of soluble factors capable of maintaining proliferation of activated B lymphocytes. Previous experiments using various culture-derived supernatants in a human system were unable to separate the activities of B cell growth factor (BCGF) and interleukin 2 (IL-2) by immunochemical means. Thus, purified factors with BCGF activity in the absence of IL-2 activity have not been available for study. In the present study, normal human peripheral blood T cells were fused with the hypoxanthine/aminopterin/thymidine-sensitive human T-leukemic cell line, CEM-6. Supernatants from the resulting hybrid cells were tested for the ability to maintain proliferation of normal human B cells in a recently described assay system for human BCGF. Hybrids demonstrating BCGF activity were cloned by limiting dilution. One hybrid clone, 2B11, continued to support proliferation of B cells in both long-term cultures and 6-d assays at a level significantly above that seen with conventionally produced growth factors. No IL-2 activity was found in the supernatant from hybrid 2B11. The hybridoma supernatant was fractionated by gel filtration, and maximum proliferation of B cells was supported by the 18-20,000 mol wt protein fraction. Thus, a human T-T cell hybridoma that has BCGF activity in the absence of any demonstrable IL-2 activity has been developed. Human T-T cell hybridomas secreting discrete immunoregulatory factors should prove to be powerful tools in dissecting the mechanisms of immunoregulation of human lymphocyte function.

B-Lymphocytes↗
PubMed1983

Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome.

The recently described acquired immune deficiency syndrome (AIDS) is characterized by the occurrence of severe opportunistic infections and an aggressive form of Kaposi's sarcoma. A variety of profound defects in cell-mediated immunity have been reported in association with the AIDS, including deficiencies in natural killer (NK) cell activity and cytomegalovirus (CMV)-specific cytotoxicity. In the present study, the in vitro effects of interleukin-2 (IL-2) and interferon beta (IFN Beta) on these abnormalities were examined to assess the potential use of these lymphokines in the immunotherapeutic treatment of this syndrome. The peripheral blood lymphocytes (PBL) from six male homosexuals with AIDS and an active CMV infection exhibited markedly depressed NK cell and CMV-specific cytotoxic lymphocyte responses compared with uninfected, heterosexual control subjects. Incubation of PBL with IFN Beta enhanced the NK cell activity and the CMV-specific cytotoxicity of only one of six and neither of two AIDS patients, respectively, while enhancing the NK cell activity of all six control subjects. In contrast, IL-2 dramatically enhanced both the NK cell and the CMV-specific cytotoxic lymphocyte activities of all of the patients. These results indicate that IL-2 can substantially potentiate the depressed cytotoxic effector functions of PBL from AIDS patients, while IFN Beta has little effect.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

We have recently noted marked differences between the in vitro responses of human B lymphocytes to stimulation with soluble antigens vs. stimulation with mitogens. In the present study, these differences were analyzed in terms of the precursor frequencies for the T cells and B cells involved and in terms of the radiation sensitivity of the T cells providing help in the two systems. Marked differences were found between antigen-induced and mitogen-induced systems with regard to T cell precursor frequencies and radiation sensitivity. In contrast, the precursor frequencies for the B cells involved in the two systems were approximately the same. In addition, having developed a system for the study of human antigen-specific B cell responses, we were interested in delineating the nature of the allogeneic effects that might be operative in this system. Marked allogeneic effects, both positive and negative, were noted in this system and will need to be taken into account in any studies that try to address the question of the genetic restriction, if any, that exists in human antigen-specific T cell-B cell collaboration. Appreciation of the marked differences between the antigen-specific and mitogen-induced activation and immunoregulation of human B cell responses will be of importance in understanding the relationship between specificity and nonspecificity of antibody production in normal and disease states.

Adolescent↗
PubMed1983

Activation and regulation of human immune responses: implications in normal and disease states.

A model of activation, proliferation, and differentiation of human lymphocyte responses is described, and the complex immunoregulatory modulation of this system discussed with regard to normal immune function and the aberrancies expressed in diseases characterized by abnormalities of immune function. Recent advances in technology of cloning and hybridizing human T cells as well as hybridizing human B cells have had a critical impact on the field of human immunobiology and have made available potentially unlimited amounts of purified antibodies and immunoregulatory factors. Of particular note has been the optimization of conditions for the production of B-cell hybridomas from human peripheral blood B cells secreting monoclonal antibody directed against predetermined antigenic specificities to which a subject has been immunized. Furthermore, the development of antigen-specific human T-cell clones has allowed a precise delineation of the genetic restriction in monocyte-T-cell interactions as well as the functional capability of T-cell subsets. Precise definition of these systems has allowed a greater understanding of the mechanisms of diseases characterized by aberrancies of immune function.

Antibodies, Monoclonal↗
PubMed1983

Bacteremia due to Mycobacterium avium-intracellulare in the acquired immunodeficiency syndrome.

The presence of Mycobacterium avium-intracellulare has frequently been demonstrated in tissue specimens from patients with the acquired immunodeficiency syndrome. The importance of this mycobacterium as a cause of constitutional symptoms and organ dysfunction has been unclear, however, because of the sparse inflammatory response evoked and the frequent concurrence of other pathogenic organisms. We detected M. avium-intracellulare in blood samples from eight patients with the acquired immunodeficiency syndrome, seven of whom had a previously recognized M. avium-intracellulare infection. Blood cultures were positive on 1 to 14 occasions over 135 days using the Dupont isolator system or the Bactec 12B medium system. Cultures were positive within 14 to 51 or 7 to 14 days with the respective techniques. The ability to rapidly isolate M. avium-intracellulare from blood may provide a useful diagnostic technique for detecting disseminated mycobacterial disease in patients with the acquired immunodeficiency syndrome as well as in other patient populations. This technique may also be useful for assessing the efficacy of drug therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1983

High incidence of free monoclonal lambda light chains in the sera of patients with Sjogren's syndrome.

Sjogren's syndrome presents a wide spectrum of disease manifestations ranging from benign to malignant lymphoproliferation. Sera from 21 patients with primary Sjogren's syndrome, 63 patients with other autoimmune rheumatic diseases, and 140 normal controls were studied by using high-resolution gel electrophoresis combined with immunofixation and specific absorption studies. Two-thirds of the sera from Sjogren's syndrome patients contained free monoclonal lambda light chains. In addition, one patient with Sjogren's syndrome and pseudolymphoma had a circulating monoclonal IgM-lambda immunoglobulin. In contrast, only 16% of the patients with other autoimmune diseases and 5% of normals had monoclonal bands; none of the other patients studied exhibited monoclonal-free lambda light chains in their serum. Our findings suggest that the monoclonal process in Sjogren's syndrome starts early in the disease process in a subset of B cells.

Antibodies, Monoclonal↗
PubMed1982

Human monoclonal anti-keyhole limpet hemocyanin antibody-secreting hybridoma produced from peripheral blood B lymphocytes of a keyhole limpet hemocyanin-immune individual.

A human IgMk monoclonal antibody, 2F7, of predetermined specificity, has been produced by the fusion of human peripheral blood lymphocytes with the nonsecreting mouse myeloma line SP-1. The heterohybridoma has remained stable for over 8 mo, with culture supernatants containing up to 30 micrograms/ml of specific IgM. The antibody has been shown to be capable of inducing a blastogenic response in the absence of antigen in the peripheral blood lymphocytes of normal subjects immune to the antigen. The ability to choose an antigen, immunize a human subject to that antigen, and then use the peripheral blood lymphocytes from that subject to produce antigen-specific human monoclonal antibodies should be of great value in a wide variety of investigative, diagnostic, and therapeutic endeavors.U

Animals↗
PubMed1981

In vitro antigen-induced, antigen-specific antibody production in man. Specific and polyclonal components, kinetics, and cellular requirements.

A highly specific and reproducible antigen-induced, antigen-specific culture and assay system for antibody production by human peripheral blood B lymphocytes has been developed. The system is clearly T cell and monocyte dependent and is independent of exogenous mitogens. The major factors in our ability to trigger specific antibody production with antigen alone have been the use of extremely low concentrations of antigen in vitro (doses several orders of magnitude below those inducing a peak blastogenic response), careful attention to in vitro cell density and culture vessel geometry, and appreciation of the kinetics of the circulating antigen-inducible B cell repertoire. A dichotomy and overlap between antigen-induced, antigen-specific and antigen-induced, polyclonal responses was observed in the study of doubly immunized individuals. Whereas antibody responses highly specific for the antigen in culture were observed under one set of culture conditions (flat-bottomed vessels, 1.5 x 10(6) cells), switching to another culture system (round-bottomed vessels, 5 x 10(5) cells) resulted in polyclonal responses to antigen. Despite these culture condition-related differences in the induction of antibody synthesis, the suppression of specific antibody production that occurred at high concentrations of antigen was specific only for the antigen in culture. The capability to easily and reproducibly look at truly antigen-induced, antigen specific antibody production should be a major tool in furthering the understanding of human B cell activation and immunoregulation.

Adolescent↗
PubMed1981

Antigen-induced in vitro antibody production in humans: a model for B cell activation and immunoregulation.

The precise events associated with B cell activation in humans are a subject of intense investigation. It has been difficult to develop an in vitro model of antigen-specific triggering of antibody synthesis by human peripheral blood mononuclear cells that is independent of exogenous mitogens. In the present study a sensitive and reproducible culture system and enzyme-linked immunosorbent assay have been established wherein antigen alone is used to trigger antigen-specific antibody synthesis by mononuclear cells from subjects immunized to keyhole limpet hemocyanin (KLH). The in vitro antigen-induced anti-KLH response is comparable in magnitude to that induced by pokeweed mitogen, is predominantly IgM in isotype, and is accompanied by a simultaneous increase in polyclonal antibody production. Anti-KLH responses were seen at in vitro KLH concentrations as low as 0.05 microgram/ml. However, concentrations of KLH greater than 5 microgram/ml resulted in profound suppression of the anti-LHL response while continuing to trigger large amounts of total polyclonal immunoglobulin synthesis. This suppression by high concentrations of antigen was also observed in pokeweed mitogen-driven anti-KLH production. These observations are consistent with previous results from the mouse model showing a close association between antigen-specific and polyclonal responses and the phenomenon of antigen-induced, antigen-specific suppression. Thus, an in vitro model of antigen induction of antigen-specific antibody synthesis in human peripheral blood mononuclear cells has been demontrated and should prove useful in exploring the mechanism of human B cell activation and immunoregulation.

Antibody Formation↗
PubMed1969

Abscission of cotton flower buds and petioles caused by protein from boll weevil larvae.

Protein extracted from boll weevil larvae causes abscission of cotton flower buds and debladed petioles. Abscission of buds is preceded by a rapid and persistent flaring of bracts; cell proliferation is induced in the abscission zone of debladed petioles. A possible mode of transmission of the agent from larva to bud tissue is discussed.

Journal Article↗