Roland H. Gisler

Characterization and Function of T Cell Fcγ Receptor

Soon after their discovery, receptors for the Fc fragment of immunoglobulins (FcR) were envisaged as key molecules regulating immune reactions, since they allow for interaction between immunocompetent cells and antibodies (reviewed by Dickler 1976). In fact, evidence increasingly in favors such receptors being expressed on subsets of all cell types that compose the immune system (Basten et al. 1972a, Yoshida & Andersson 1972. Unkeless & Fisen 1975) and that FcR exist for all immunoglobulin classes (Dickler & Kunkel 1972, Moretta et al. 1975, Gonzalez-Molina et al. 1977, Gupta et al. 1979) and for some subclasses (Basten et al. 1972b, Anderson & Grey 1974, Krammer et al. 1975, Walker 1976, Heusser et al. 1977, Unkeless 1977, Haeffner-Cavaillon et al. 1979). Thus, maerophages (Unkeless & Fisen 1975, Heusser et al. 1977), B cells (Basten et al. 1972a, Dickler & Kunkel 1972), K cells (MacLennan 1972, Perlmann et al. 1972), some T cells (Yoshida & Andersson 1972, Fridman & Golstein 1974, Van Boxel & Rosenstreich 1974, Soteriades-Vlachos et al. 1974) and NK cells (Peter et al. 1975, Herberman et al. 1979) express FeR for IgG (FcyR)A subset of human (Moretta et al. 1975) and possibly also murine (Lamon et al. 1975) T cells bear FcR for IgM (Fc)iR) and the existence of a similar receptor on activated maerophages has also been suggested (Roubin et al. 1979). Finally, some T cells have been found to express FcR for IgA (Gupta et al. 1979, Lumetal. 1979) and IgF (FCER; Yodoi & Ishizaka 1979).

Hormonal regulation of the immune response. II. Influence of pituitary and adrenal activity on immune responsiveness in vitro.

Abstract Exposure of mice to acceleration stress, ether anesthesia or injection of adrenocorticotropic hormone (ACTH) resulted in a transitory increase of plasma corticosterone concentrations. Spleen cells explanted at the moment of increased levels of corticosteroids reacted poorly to antigen in vitro. Adrenalectomy of the cell donors did not affect the immune reactivity of spleen cell cultures, nor did ACTH show any effect in adrenalectomized mice. On the other hand, hypophysectomy of the cell donors led to a persistent depression of the immune response. Treatment of hypophysectomized animals with somatotropic hormone (STH) prior to cell culture resulted in an almost normal immune capacity. Moreover, subsequent ACTH treatment no longer impaired immune reactivity, although it effectively increased plasma corticosterone levels. It is concluded that recovery from corticosteroid-induced depression of immune reactivity is accelerated in the presence of somatotropic hormone. In hypophysectomized animals exogenous somatotropic hormone can interfere with the effect of increased endogenous corticosterone.

Stress and the Hormonal Regulation of the Immune Response in Mice

Exposure of mice to different types of acute stress (acceleration, ether anesthesia, restraint, overcrowding) or injection of adrenocorticotropic hormone resulted in an increase of plasma corticostero

Hormonal regulation of the immune response: I. Induction of an immune response in vitro with lymphoid cells from mice exposed to acute systemic stress

Abstract The effect of exposure of mice to stress, by acceleration and ether anesthesia, on in vitro immune responsiveness of their spleen or peritoneal cells, has been studied in different mouse strains. Stress 6, 16, or 24 hr prior to stimulation of explanted lymphoid cells with SRBC in vitro leads to suppression of immune reactivity, whereas a time interval of only 15 min resulted in impaired or normal or even enhanced production of PFCs. By 72 hours, normal levels of immune responsiveness were reestablished. Similar findings were obtained with peritoneal and spleen cells from mice that had been freshly shipped to the laboratory and not given time to acclimatize. The onset and the degree of altered immune responsiveness were related to the mouse strain used and also to the experimental conditions. Histological examination showed a close relationship between depletion of small lymphocytes in the peripheral areas of the follicles and in the marginal zones of the spleen and diminished immune reactivity of the corresponding cell suspensions in vitro .

Inhibition of the in vitro 19S and 7S antibody response by immunoglobulin-binding factor (IBF) from alloantigen-activated T cells☆

Abstract A soluble factor secreted by alloantigen-activated mouse T cells which binds to the Fc fragment of IgG and inhibits complement activation by IgG (immunoglobulin-binding factor, IBF) suppressed the in vitro 19S and 7S antibody response by mouse spleen cells to T-dependent as well as T-independent antigens. IBF inhibited the 19S plaque response best when it was added late during PFC generation (between 48 and 72 hr). On the other hand, when it was left in cultures for up to 60 hr and then removed, antibody synthesis was not inhibited. However, its presence for only 2 hr starting after 72 hr of incubation was sufficient to inhibit PFC formation. The suppressive activity of IFB could be neutralized by adding aggregated mouse IgG prior to the critical stage around 72 hr. These data favour the view that IBF could be a suppressive T cell factor and point to the possibility that IBF may act on already triggered B cells during their final differentiation to active PFC.

Modulation of myelopoiesis by different bacterial cell-wall components: Induction of colony-stimulating activity (by pure preparations, low-molecular-weight degradation products and a synthetic low-molecular analog of bacterial cell-wall components) in vitro

Abstract Chemically pure preparations of three structurally unrelated components of the cell wall of gram-negative bacteria (BCWC), lipid A, outer-membrane lipoprotein, and murein, were tested for lymphocyte mitogenicity and the ability to induce colony-stimulating activity (CSA) in various serum-free tissue-culture systems. All three components were B-cell mitogens and induced CSA in spleen-cell cultures. However, in lymphnode-cell cultures the concentrations of these agents required for either mitogenicity or CSA induction differed markedly. Moreover, in contrast to thymidine incorporation, CSA induction was not influenced by pre-irradiation of the cells. Conversely, after removal of phagocytic cells with the iron-magnet technique, CSA was no longer inducible by BCWC, while lymphocyte proliferation was barely impaired. All three BCWC readily induced CSA release in cultures of adherent peritoneal cells without influencing the release of a cytoplasmic enzyme. BCWC-dependent CSA release from adherent peritoneal cells was not influenced by pretratment of the cultures with anti-immunoglobulin, but completely suppressed by preincubation with anti-macrophage-1.2 alloantiserum and complement. CSA induction in macrophage cultures was also achieved with a low-molecular-weight synthetic muramyldipeptide and degradation products of lipoprotein. The results suggest that the induction of CSA is not directly related to the mitogenic, immunogenic, or antigenic properties of the BCWC, but that BCWC-mediated CSA production is caused by a direct “hormone-like” interaction of the agents with mature macrophages.

New developments in drugs enhancing the immune response: activation of lymphocytes and accessory cells by muramyl-dipeptides

Recently, stimulation of host defence mechanisms has become a major goal of pharmacotherapeutic research. Immunopotentiating compounds exert their effects in different ways. On the one hand, they may enhance non-specific effector mechanisms operative in the resistance of infectious agents and to neoplastic cells. On the other hand, they may non-specifically increase specific immune responses elicited by the recognition of antigenic determinants. Of course, the two mechanisms operative in the resistance to infectious agents and to neoplastic cells. On may be mediated by the pharmacological activation of common target cells, that is macrophages and other accessory cells, such as polymorphonuclear leucocytes.

A three-cell mosaic culture: In vitro immune response by a combination of pure B- and T-cells with peritoneal macrophages

Abstract Lymph node cell suspensions from BD 2 F 1 and nu/+ mice contained very low numbers of macrophages and failed to produce PFC upon exposure to sheep erythrocytes if cultured alone. Addition of 99%-pure, attached mononuclear peritoneal phagocytes resulted in the development of PFC comparable to that seen with spleen cells. Spleen cells from congenitally athymic nu/nu mice were lacking θ-positive cells and responded to sheep erythrocytes only if cortisone-resistant nu/+ thymus cells were added. Lymph node cells from nu/nu mice (devoid of both θ-positive cells and phagocytes) responded in culture provided both cortisone-resistant thymus cells and purified macrophages from nu/+ donors were present. None of the three components displayed any activity if cultured alone. Omission of only one component of the three-cell system also greatly diminished the response. Full reactivity of the composite cultures could be achieved by the addition of a relatively small proportion of cortisone-resistant thymus cells. The results are discussed in terms of nonspecific T-cell activation and of a three-cell model of the in vitro immune response to sheep red cells.

Role of Macrophages in the in Vitro Induction and Regulation of Antibody Responses

For more than fifty years, macrophages were only considered to take part in non-specific immunity processes such as phagocytosis and the degradation of foreign material. However, in 1967 Mosier demonstrated that adherent cells with the characteristics of macrophages were also involved in the specific immune response. Since then, immunological interest in macrophages has increased enormously, but many mysteries about this cell remain to this day.

SUPPRESSION OF “IN VITRO” ANTIBODY SYNTHESIS BY A T CELL PRODUCT. ITS RELATION WITH THE Fc RECEPTOR OF ACTIVATED T CELLS,

Publisher Summary Activated T cells (ATC) release a variety of soluble factors, which have been defined by their biological activities. They act either as effectors of “in vitro” cell-mediated reactions or as cooperative molecules-amplifiers or suppressors—in the elicitation of an antibody response. Among the suppressor factors, some are antigen-specific while others do not show any specificity. The chapter describes the kinetics of action of IBF on primary and secondary immune responses “in vitro” and shows that IBF acts on the late phase of the response. It discusses the relationship between IBF and the Fc receptors of ATC; the same subpopulation of ATC that bears the receptor produces the factor and that there exists a close relationship between the time-dependent disappearance of Fc receptors from the cell membrane and the release of IBF into the supernatant.