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S Gillis

Publications and source records attributed to S Gillis.

At least 217 records · Page 12Linked to original sources
PubMed1983

Interleukin 2 is not sufficient for the continuous growth of cloned NK-like cytotoxic cell lines.

Interleukin 2 (IL 2) has been strongly implicated as the agent responsible for the continuous growth of T cell lines in vitro. In the present study we confirmed that IL 2 alone could support the growth of a widely used cytotoxic T cell line. In contrast, we found that IL 2 was not sufficient to support the long-term growth of cloned NK-like cytotoxic lymphocyte cell lines. Whereas such lines would grow indefinitely in concanavalin A-induced mouse spleen cell supernatant, they would only grow for short periods (2 to 3 days) in the IL 2-containing supernatant of phytohemagglutinin-stimulated LBRM-33 tumor cells, or in IL 2 partially purified from spleen cell or LBRM-33 supernatants. The addition of concanavalin-A or interferon (type beta or gamma) to these supernatants did not improve growth. By contrast, the NK-like cells proliferated equally well in a short-term (24-hr) assay, irrespective of the source of IL 2 (spleen or LBRM-33 supernatant, or partially purified IL 2). Furthermore, the NK-like cells readily depleted IL 2 from the medium, either during growth at 37 degrees C or by absorption at 4 degrees C. It is concluded that at least some cytotoxic cell lines require both IL 2 and other, as yet unidentified, spleen cell-derived factors for long-term growth.

Animals↗
PubMed1982

Definition of T cell idiotypes using anti-idiotypic antisera produced by immunization with T cell clones.

Alloreactive T cell clones with distinct specificities were used to raise anti-idiotypic antisera via an F1 anti-(parent anti-F1) protocol. Antisera were raised that could stimulate the proliferation of the appropriate T cell clone, but not other clones. The active fraction of the antisera for T cell proliferation was immunoglobulin. In addition to proliferation, an anti-idiotypic antiserum could induce the appropriate T cell clone to secrete substantial amounts of interleukin 2 (IL-2). Production of IL-2 appeared independent of the involvement of accessory cells. These accessory cells may be unnecessary for IL-2 production in our assay, or their effect may be produced by anti-idiotype. Thus, anti-idiotype may provide two or more specific T cell signals.

Animals↗
PubMed1982

Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2.

Spleen cells from C57BL/6 mice immunized in vivo with a syngeneic Friend virus-induced leukemia, FBL-3, were specifically activated by culture for 7 d with FBL-3, then nonspecifically induced to proliferate in vitro for 12 d by addition of supernatants from concanavalin A-stimulated lymphocytes containing interleukin 2 (IL-2). Such long-term cultured T lymphocytes have previously been shown to specifically lyse FBL-3 and to mediate specific adoptive therapy of advanced disseminated FBL-3 when used as an adjunct to cyclophosphamide (CY) in adoptive chemoimmunotherapy. Because the cultured cells are dependent upon IL-2 for proliferation and survival in vitro, their efficacy in vivo is potentially limited by the availability of endogenous IL-2. Thus, the aim of the current study was to determine whether exogenously administered purified IL-2 could augment the in vivo efficacy of long-term cultured T lymphocytes. Purified IL-2 alone or as an adjunct to CY as ineffective in tumor therapy. However, IL-2 was extremely effective in augmenting the efficacy of IL-2-dependent long-term cultured T lymphocytes in adoptive chemoimmunotherapy. The mechanism by which IL-2 functions in vivo is presumably by promoting in vivo growth and/or survival of adoptively transferred cells. This assumption was supported by the findings that IL-2 did not enhance the modest therapeutic efficacy of irradiated long-term cultured cells that were incapable of proliferating in the host and was ineffective in augmenting the in vivo efficacy of noncultured immune cells that are not immediately dependent upon exogenous IL-2 for survival.

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

Ia-dependent interleukin 2 production in syngeneic cellular interactions.

In the murine syngeneic mixed lymphocyte response (SMLR), the co-culture of nylon wool-nonadherent spleen cells or young (4 to 6-day-old) thymocytes with syngeneic nylon wool-adherent adult spleen cells, results in proliferation and Interleukin 2 (IL 2) production. In both the thymus and spleen SMLR, proliferation and IL 2 production are the function of Lyt-1+2-3- (Lyt-1) responder cells and require the expression of IA (IB) and/or IE cell surface antigens on the stimulator cell. IL 2 production in both spleen and thymus SMLR is independent of heterologous serum factors (i.e., fetal calf serum), which, however, influences the magnitude of the in vitro proliferation. The IL 2-producing cell in spleen is capable of self-renewal in the absence of the thymus; it is detectable 6 to 7 mo after adult thymectomy. These results suggest the in vitro SMLR may measure a cellular interaction between the Lyt-1 subset of T cells and self Ia antigens on macrophage-like cells that produces IL 2 in an antigen-independent fashion. This interaction may have physiologic significance in the expression and regulation of T cell function.

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

Interleukin 2, production in the syngeneic mixed lymphocyte reaction.

In the syngeneic mixed lymphocyte reaction, Ly 1 cells proliferate following stimulation with Ia-positive macrophage-like cells. The proliferation is accompanied by the release of interleukin 2 into the medium. Both the proliferation and interleukin 2 production are dependent on the expression of Ia antigenic determinants, as the addition of haplotype-specific anti-Ia antisera to the cultures inhibits both parameters.

Animals↗
PubMed1981

T-cell growth factor (interleukin 2) and terminal transferase activity in human leukemias and lymphoblastic cell lines.

Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.

Acute Disease↗
PubMed1981

T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation.

Several laboratories have recently demonstrated that the requirement for macrophages in mitogen-induced production of murine T-cell interleukin 2 (IL-2; formerly referred to as "T-cell growth factor") could be circumvented by using the macrophage-derived peptide interleukin 1 (IL-1; formerly referred to as "lymphocyte-activating factor"). Using two cloned T-cell lymphomas, we investigated the mechanism through which IL-1 exerted its effect on IL-2 production. One of the cell lines used (LBRM-33 5A4) produces large concentrations of IL-2 upon mitogen stimulation, whereas the second (LBRM-33 1A5) is incapable of producing IL-2 in response to mitogen. It was observed that addition of purified IL-1 to nonproducer 1A5 cells converted them to a state in which subsequent mitogen stimulation triggered production of IL-2. The concentration of IL-2 produced by IL-1 treated 1A5 cells was equivalent in magnitude to that generated by mitogen-stimulated 5A4 cells (500-1000 units/ml, or approximately 1000 times the concentration of IL-2 contained in conventional preparations of murine mitogen-conditioned medium). The observations that (i) brief exposure to IL-1 was sufficient for 1A5 cell conversion to IL-2 production and (ii) IL-1 could actively be absorbed from culture medium by live or fixed 1A5 cells led us to propose the existence of IL-1 receptors on responsive 1A5 cells. On the basis of these experiments, we have postulated that IL-1 mediates its effect on immune reactivity (enhancement of thymocyte mitogenesis and induction of antibody and cytotoxic T cell responses) by maturation of a subset of immature T cells to the point where they are capable of IL-2 production. Subsequent release of IL-2 after ligand activation allows for clonal expansion of activated T cells which mediate particular effector functions.

Animals↗
PubMed1981

Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans.

Human lymphocytes from elderly and young donors were cultured with phytohemagglutinin (PHA) or concanavalin A. Cultures from old donors produced less T cell growth factor (TCGF) and incorporated less tritiated thymidine (3H-Tdr) than did similar cultures from young donors in the presence of either mitogen. Furthermore, the response of lymphocytes from elderly donors to TCGF was impaired. Thus, PHA-activated T cells from aged donors showed no increase tritiated thymidine incorporation when incubated with exogenous human TCGF. In contrast, addition of exogenous human TCGF to PHA-activated peripheral blood leukocytes from younger individuals increased tritiated thymidine incorporation by 30-50%. The impaired response to TCGF was associated with decreased binding of TCGF by PHA-activated cells from old donors. TCGF production or responsiveness was not associated with the presence of "suppressor" activity in elderly T cell preparations. These studies suggest a possible molecular mechanism for the impaired proliferative response of elderly human T cells. These data lend support to the hypothesis that defects in the capacity to either produce or respond to TCGF may be a fundamental cause of immune deficiency.

Adult↗