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K H Grabstein

Publications and source records attributed to K H Grabstein.

82 records · Page 5Linked to original sources
PubMed1987

Regulation of murine T cell proliferation by B cell stimulatory factor-1.

The proliferation of mitogen-activated primary T cells, antigen-activated memory T cells from mixed leukocyte culture, and antigen-dependent alloreactive T cell clones in response to purified murine recombinant B cell stimulatory factor-1 (also known as interleukin 4) was examined. We found that B cell stimulatory factor-1 (BSF-1) stimulated optimal proliferation of these T cells only after their recent activation by antigen or mitogen. Analysis of cell surface BSF-1 receptor expression indicated that although T cell activation is accompanied by a small increase in BSF-1 receptor expression, the cells also express BSF-1 receptors prior to activation at a time when they do not proliferate in response to BSF-1. BSF-1 was as effective a stimulus as interleukin 2 for inducing proliferation of the Lyt-2+ subpopulation of concanavalin A-activated murine spleen cells and an alloreactive cytolytic T cell clone. However, the L3T4+ subpopulation of concanavalin A-activated spleen and an alloreactive helper T cell clone were less responsive to BSF-1 than to interleukin 2. Taken together, the data indicate an important role for BSF-1 in the regulation of normal T cell proliferation.

Animals↗
PubMed1987

Localization of human mononuclear cell interleukin 1.

The detection and localization of interleukin (IL) 1 in human monocytes was carried out by flow cytometry using monoclonal antibodies to IL-1 alpha and IL-1 beta proteins. IL-1 alpha was detected on the surface of monocytes and the surface expression increased following lipopolysaccharide activation. No demonstrable IL-1 beta protein could be observed on the cell surface by antibody staining, while both IL-1 alpha and IL-1 beta could be visualized intracellularly by the appropriate monoclonal antibodies following acetone permeabilization of the monocytes. Further experiments with cell associated IL-1 revealed that most of the biological activity of human monocytes could be inhibited by affinity purified polyclonal antibodies to IL-1 alpha protein, whereas no inhibitory activity was observed with IL-1 beta specific antibodies. These data support the hypothesis that a differential localization of IL-1 alpha and IL-1 beta exists within human blood-derived monocytes.

Antibodies, Monoclonal↗
PubMed1986

Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor.

Monocytes are a subpopulation of peripheral blood leukocytes, which when appropriately activated by the regulatory hormones of the immune system, are capable of becoming macrophages--potent effector cells for immune response to tumors and parasites. A complementary DNA for the T lymphocyte-derived lymphokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), has been cloned, and recombinant GM-CSF protein has been expressed in yeast and purified to homogeneity. This purified human recombinant GM-CSF stimulated peripheral blood monocytes in vitro to become cytotoxic for the malignant melanoma cell line A375. Another T cell-derived lymphokine, gamma-interferon (IFN-gamma), also stimulated peripheral blood monocytes to become tumoricidal against this malignant cell line. When IFN-gamma activates monocytes to become tumoricidal, additional stimulation by exogenously added lipopolysaccharide is required. No such exogenous signals were required for the activation of monocytes by GM-CSF.

Cell Line↗
PubMed1982

Prevention of the in vitro myelosuppressive effects of glucocorticosteroids by interleukin 1 (IL 1).

We investigated the effects of dexamethasone on the formation of granulocyte/macrophage colonies by murine bone marrow cells cultured with colony-stimulatory factors (CSF) in semisolid agar. Dexamethasone (10(-7) M) completely inhibited the formation of colonies in response to L929 CSF but had no effect on the response to CSF in the culture supernatants of the murine macrophage cell line, PU5-1.8. We postulated that a cofactor, interleukin 1, present in the PU5-1.8 supernatants was responsible for protecting colony formation against steroid suppression. Interleukin 1, isolated from culture supernatants of PU5-1.8 and from culture supernatants of human acute monocytic leukemia cells, blocked the inhabitory effects of dexamethasone on colony formation in response to L929 CSF. Moreover, dexamethasone inhibited colony formation in response to PU5-1.8 culture supernatants when interleukin 1 was absent. We also examined interleukin 2 for possible protective effects. Although crude interleukin 2 preparations (supernatants of spleen cells cultured with concanavalin A) blocked dexamethasone inhibition, purified interleukin 2 had no protective effects. These data indicate that interleukin 1 protects colony formation by a pathway that is independent of interleukin 2 and that supernatants of spleen cells activated with concanavalin A probably contain significant amount of interleukin 1.

Animals↗
PubMed1980

Prevention of the immunosuppressive effects of glucocorticosteroids by cell-free factors from adjuvant-activated accessory cells.

Cultured mouse spleen cells are protected from the immunosuppressive effects of glucocorticosteroid hormones by prior treatment with bacterial adjuvants. The mechanisms by which such protection is acquired were further invgestigated in this study. Cell-free factors, termed glucocorticosteroid response modifying factors (GRMF), were obtained from the supernatant fluid of normal resident murine peritoneal macrophages activated in vitro by treatment with lipopolysaccharide. These factors provided protection against steroid immunosuppression in a dose dependent fashion. Two-step experiments show that GRMF treatment results in the recovery of significant amounts of T helper activity which otherwise is suppressed by steroids. Factors with similar biologic activities were also obtained from murine monocytic cell lines. The possible mechanisms by which GRMF protects the immune response are discussed.

Animals↗
PubMed1977

Sera and the in vitro induction of immune responses. III. Adjuvant obtained from gliding bacteria with properties distinct from enteric bacterial lipopolysaccharide.

We have extended our studies on the role of bacterial contamination in the generation of fetal calf sera which support primary in vitro humoral responses by cultured mouse spleen cells. Gram-negative, gliding bacteria were isolated from a strongly supportive sample of fetal calf sera. Medium conditioned by the growth of these microorganisms had strong adjuvant effects in cultures of mouse spleen cells supplemented with a non supportive, deficient sera. The adjuvant and mitogenic activities of the bacterial conditioned medium were then compared to those of bacterial lipopolysaccharide from Salmonella typhosa 0901 in cultures of LPS responder and LPS nonresponder spleen cells. From the results of these comparative studies, we conclude that the active factor(s) obtained from the gliding bacteria is an adjuvant with properties very distinct from those of highly purified enteric bacterial LPS.

Adjuvants, Immunologic↗
PubMedDate not supplied

Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor.

The growth and differentiation of cytolytic T lymphocytes (CTL) is regulated by soluble growth hormones, of which interleukin-2 (IL-2) is considered to be of prime importance. Here we report that the lymphokine B-cell stimulatory factor (BSF-1 or interleukin-4) also has profound effects on the generation of these functionally active T cells. In particular, BSF-1 acts as a potent helper factor for the generation of CTL in primary mixed leukocyte culture (MLC) and induces cytolytic activity in in vitro primed, MLC memory populations. Direct comparison of purified recombinant BSF-1 and IL-2 reveals BSF-1 to be the more potent CTL helper factor in primary MLC. Interestingly, the two lymphokines differed in that IL-2, but not BSF-1, induced a lytic population in cultures of unprimed cells without an overt antigenic stimulus. Collectively, our data provide a direct demonstration of a heretofore undefined mechanism by which CTL activation and amplification can occur.

Animals↗
PubMedDate not supplied

Interleukin-4 (B-cell stimulatory factor-1) augments the in vivo generation of cytotoxic cells in immunosuppressed animals.

Thymus-derived lymphocytes (T cells) are thought to play an important role in the recognition and destruction of neoplastic cells in the host. This principle has provided a foundation for the establishment of therapy with T-cell-stimulating lymphokines, notably interleukin-2, as an approach to the eradication of certain malignancies. Another lymphokine, B-cell-stimulatory factor-1 (BSF-1), also known as IL-4, has also been shown to be capable of inducing T-cell proliferation and cytolytic activity in vitro. We demonstrate herein that in immunosuppressed mice, in vivo IL-4 administration enhances the ability of treated animals to generate cytotoxic T lymphocytes directed against an allogeneic tumor challenge. Moreover, IL-4 is approximately 25 times more effective, on a weight basis, than is IL-2 in augmenting cytotoxic T-lymphocyte activity. This difference in efficiency between the two lymphokines may be partly due to the in vivo half-life. We have found that IL-4 has a serum half-life of 19 +/- 2 min following intravenous administration, in contrast to the half-life of IL-2, which has been reported to be 3.7 min +/- 0.8. These results are not only of interest for our basic understanding of the physiological role of IL-4 but may have immediate importance in clinical settings where lymphokine therapy is contemplated.

Animals↗