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Biomedical subjects

C S Henney

Publications and source records attributed to C S Henney.

At least 37 records · Page 2Linked to original sources
PubMed1982

NK cell-target interactions: approaches towards definition of recognition structures.

NK cells lyse an uncommonly wide range of cell types, implying either that they (the NK cells) have clonally distributed receptors each of which is capable of interacting with a very limited number of cell types or, alternatively, that susceptible target cells share a common characteristic. A number of experimental approaches have suggested that the cytotoxic 'specificity' of NK cells is not clonally distributed. Thus, clones of NK cells, established from mouse spleen cell suspensions, showed no greater restriction in the spectrum of target cells which they could lyse, than did the parent spleen cell populations from which they were derived. It seems likely therefore that the wide range of target cell types that can be lysed by NK cells share common cell surface characteristics which render them susceptible. As lysis results from membrane-membrane interactions, it seemed logical that a search for 'hallmarks' of NK susceptibility should begin with a detailed examination of the plasma membrane of susceptible cells. Analysis of one pair of lymphoma cell variants, selected on account of their markedly different susceptibility to NK cells, suggests that cell surface glycoconjugates may be of significance in determining those effector cell-target cell interactions that lead to lysis. This review outlines attempts to characterize such glycoconjugates.

Animals↗
PubMed1982

Display of the neutral glycolipid ganglio-n-tetraosylceramide (asialo GM1) on cells of the natural killer and T lineages.

Analysis was made of the display of the neutral glycolipid asialo GM1 on cells involved in the differentiation and expression of natural killer (NK) and T cell-mediated cytotoxicity in vitro. Removal of asialo GM1-bearing cells from CBA spleens, by treatment with a specific rabbit antibody in the presence of complement, led not only to the abrogation of NK cell activity but also to the lack of responsiveness of such populations to polyinosinic: polycytidylic acid (poly I:C) and to interferon, indicating that both NK cells and interferon-responsive cells of the NK cell lineage bear asialo GM1. Cytotoxic T lymphocytes (CTLs) induced by mixed lymphocyte culture in vitro were unaffected by treatment with antiasialo GM1 serum in the presence of complement, but normal spleen cells subjected to this treatment failed to mount CTL responses to alloantigen, even in the presence of an exogenous source of Interleukin-2 (IL-2). Furthermore, spleen cell populations depleted of asialo GM1-bearing cells showed a decreased ability to produce IL-2 in response to mitogenic stimulation.

Animals↗
PubMed1982

Cytokine-dependent thymocyte responses: characterization of IL 1 and IL 2 target subpopulations and mechanism of action.

The responsiveness of murine thymocytes to T cell mitogens was examined in the presence of highly purified preparations of IL 1 and IL 2. Fractionation of thymocytes by selective agglutination with peanut lectin (Arachius hypogeae) resulted in separation of two cell populations, each of which mediated distinctive responses to cytokine stimulation. The majority of thymus cells, agglutinated by the lectin (PNA+), were found to be unresponsive to mitogen in the presence of the macrophage-derived factor, IL 1; but showed marked proliferation when stimulated by mitogen in concert with the T cell-derived factor, IL 2. The nonagglutinated fraction, (PNA- cells) demonstrated substantial levels of proliferation after stimulation with mitogen in the absence of any exogenous factors. Moreover, IL 1 alone was highly mitogenic for PNA-thymocytes. This stimulation was further shown to result in the subsequent release of IL 2, as assessed by both the detection of IL 2 by lymphokine-dependent T cell lines and the inhibition of IL 1-dependent mitogenesis by the presence of anti-IL 2 monoclonal antibody. These results further substantiate the important immunoregulatory nature of these proteins and elucidates the possible role of these substances in the ontogeny of T cell responsiveness.

Animals↗
PubMed1981

Monoclonal antibody directed against interleukin 2. I. Inhibition of T lymphocyte mitogenesis and the in vitro differentiation of alloreactive cytolytic T cells.

Our recent studies have detailed the generation of B cell hybridomas whose IgG product significantly inhibits interleukin 2 (IL-2)-dependent T cell replication. Given the capacity of such hybridoma antibody to interfere with the activity of mouse, rat, and human IL-2, we asked whether anti-IL-2 IgG would mediate similar inhibitory effects on other in vitro immune responses. In this communication, we report that addition of purified anti-IL-2 monoclonal antibody to either mitogen- or alloantigen-stimulated spleen cells exerted markedly deleterious effects on both resultant T cell proliferation and the generation of cytolytic effector cells. These results provide serological evidence in support of the integral role that IL-2 plays in controlling antigen/mitogen-induced T cell proliferation and serves further to define the ability of monoclonal antibody against IL-2 to function as an immunosuppressive agent.

Animals↗
PubMed1981

The differentiation of cytotoxic T cells in vitro. IV. Interleukin-2 production in primary mixed lymphocyte cultures involves cooperation between Qa-1+ and Qa-1- "helper" T cells.

Studies with C57BL/6-TIaa mice have established that both Qa-1+ and Qa-1- helper T cells are required for the optimal production of Interleukin 2(IL-2) activity in primary MLC. This was established both by depletion of Qa-1 bearing cells by treatment of responder cells with anti-Qa-1 serum in the presence of complement and by positive selection (using FACS II analysis) of those cells displaying Qa-1. Furthermore, microfluoremetry revealed that the great majority of C57BL/6-TIaa and of A/J splenic T cells bore Qa-1 alloantigen but that only those with the highest antigen density were susceptible to complement-mediated lysis.

Animals↗
PubMed1981

The role of interleukin-2 (IL-2) in the differentiatin of cytotoxic T cells: the effect of monoclonal anti-IL-2 antibody and absorption with IL-2 dependent T cell lines.

A variety of approaches, including the use of a monoclonal antibody, have indicated that the lymphokine Interleukin 2 is a necessary and sufficient mediator for initiating cytotoxic T cell differentiation in vitro. Mitogen (Con A, PHA) stimulation of spleen cells and K/D or I region stimulation in primary MLC all led to IL-2 production, as measured by the growth of an IL-2 dependent T cell clone, and to the production of a "helper" factor necessary for cytotoxic T lymphocyte (CTL) differentiation against metabolically inactivated stimulator spleen cells. Several lines of evidence suggested that the IL-2 activity and CTL "helper" activity were due to a single molecular entity. These included the observations that: i) There was a linear relationship (R = 0.99) between IL-2 activity and relative CTL "helper" activity regardless of the preparation used (purified IL-2; MLC, or mitogen-induced supernatants). ii) Absorption of MLC supernatants with T cell "blasts" or with IL-2 dependent T cell lines concomitantly removed both IL-2 and CTL "helper" activities. iii) IL-2 activity purified by isoelectric focusing, or by polyacrylamide gel electrophoresis, displayed CTL "helper" activity. iv) Both CTL "helper" and IL-2 activities were neutralized by a monoclonal antibody directed against IL-2.

Absorption↗
PubMed1981

The biochemical and biological characterization of lymphocyte regulatory molecules. VI. Generation of a B cell hybridoma whose antibody product inhibits interleukin 2 activity.

In attempts to generate monoclonal antibodies with reactivity directed against the lymphokine Interleukin 2 (IL-2, T cell growth factor), spleen cells harvested from BALB/c mice previously immunized with rat IL-2 were fused with the BALB/c myeloma SP2. Several of the resultant hybrid cell lines secreted a product that significantly neutralized (greater than 50%) IL-2--dependent T cell proliferation. Several lines of evidence suggested that the inhibitory activity was associated with a monoclonal IgG antibody directed against IL-2 determinants. First, passage of cloned hybrid cell culture supernatants through a protein A-coupled Sepharose column yielded purified immunoglobulin G fractions that inhibited mouse, rat, and human IL-2 activity. Secondly, hybridoma-derived IgG, in concert with lyophilized Staphylococcus aureus, was capable of precipitating both "cold" and intrinsically labeled IL-2 activity. Finally, Sepharose conjugated with purified IgG fractions provided on extremely reactive IL-2 absorption matrix. These results suggest that monoclonal antibodies directed against IL-2 determinants may eventually provide new detection assays for IL-2 and allow affinity chromatography to be employed for the isolation of this lymphokine.

Animals↗