Interactions between retinal glial cells and immune mononuclear cells.
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Animals↗
Biomedical subjects
R R Caspi
Publications and source records attributed to R R Caspi.
Long-term culture of Muller cells from adult rats in the presence of activated lymphocytes/monocytes products.
A method for the culture of retinal Muller cells from adult rats is described. Whereas isolated Muller elements did not grow in a medium composed of MEM + 10% FBS, the addition of supernatant from mitogen activated spleen cells induced a strong proliferative response. The factor(s) responsible for that growth were not species specific, as mouse spleen cells conditioned medium was also an effective stimulant. The highly significant degree of DNA synthesis induced by the supernatant from an S-antigen specific T-helper cell line (reacting to the retinal antigen presented on APC) indicates that the growth promoting activity is not restricted to mitogen driven spleen cells. It is suggested that products of inflammatory cells secreted in the course of intraocular immune processes may contribute to the formation of epiretinal membranes. These products also induced the expression of Ia surface antigens by Muller cells, supporting the hypothesis of a possible involvement in local immune reactions.
Animals↗
Evidence for the existence of an IL-2-like lymphocyte growth promoting factor in a bony fish, Cyprinus carpio.
Activity promoting the growth of carp T-like cells has been found in supernatants of mitogen (PHA)- and alloantigen (MLR)-stimulated carp leukocyte cultures. Activity level in culture supernatants was elevated by phorbol myristate acetate. Proliferation of carp T-like lymphoblasts was also promoted in the presence of Il-2-containing supernatants of mammalian origin. The significance of these findings is discussed.
Animals↗
Heterogeneity of mitogen-responsive lymphocytes in carp (Cyprinus carpio).
Peripheral blood leukocytes (PBL) of carp respond in vitro to a variety of phytomitogens, shown to be T-cell specific or B-cell specific in mammalian systems. Some basic differences have been observed in the proliferative response of carp PBL to PHA (phytohemagglutinin), ConA ( concanvalin A) and LPS (lipopolysaccharide): (1) The response to PHA and ConA was found to be highly dependent upon the continuous presence of mitogen in the medium, in contrast to LPS, where after the initial stimulation, cells could continue to proliferate for several days without mitogen. (2) Lymphoblasts grown in long term culture with either PHA or Con A could be transferred into medium containing the other mitogen without impairing cell proliferation, but cell growth was reduced to background level following transfer into LPS-containing medium. LPS grown cells continue to proliferate independently of the mitogen content of the medium. (3) Co-stimulation with LPS+PHA or LPS+ConA results in a synergistic response, while co-stimulation with PHA+ConA results in inhibition of DNA synthesis. (4) Several morphological differences have been observed between cells proliferating in the presence of PHA and those proliferating in the presence of LPS. It is suggested that while the PHA and ConA responsive cells may belong to the same lymphocyte subpopulation, they are distinct from the LPS-responsive subpopulation.
Animals↗
The mixed leukocyte reaction (MLR) in carp: bidirectional and undirectional MLR responses.
Two-way and one-way mixed leukocyte reaction (MLR) was demonstrated in peripheral blood leukocytes (PBL) of carp. Primary two-way MLR in randomly selected donor pairs were highly variable. Weak primary responses could be strongly augmented by mutual in vivo priming of the reacting donors. One-way MLR was performed using irradiated (16,000 R) allogeneic PBL as stimulators. Reciprocal responses of randomly paired donors were usually unequal, suggesting the usefulness of this method for genetic analysis of MLR-recognized histocompatibility antigens in carp. Kinetics of the primary and secondary two-way MLR were studied, as well as the kinetics of primary one-way MLR against pooled allogenic stimulator cells.
Animals↗
Specific activity of carp antisera against beta 2-microglobulin (beta 2m) and evidence for a beta 2m homologue in carp (Cyprinus carpio).
Antisera against rabbit and human beta 2-microglobulin were produced in carp (Cyprinus carpio). These antisera were found to be specific for beta 2m, and detected beta 2m epitopes in various vertebrates including guinea-pig, cow, mouse, rat, dog, horse, cat, sheep, goat, parrot, chicken and frog. In addition, these antisera were also inhibited by an extract from oyster. The differences between the reactivity of these two antisera and the ability of the anti-rabbit beta 2m to distinguish between mouse and rat beta 2m's suggested that the carp itself carries beta 2m epitopes. This hypothesis was corroborated by the ability of a variety of mammalian anti-beta 2m antisera to induce a mitogenic response in carp leukocytes. Finally, a rabbit antiserum against dog beta 2m was shown to precipitate a low molecular weight molecule from carp leukocyte extract. This molecule is likely to represent the carp homologue of mammalian beta 2m.
Animals↗
Non-immunological recognition and killing of xenogeneic cells by macrophages. III. Destruction of fish cells by murine macrophages.
Non-immune non-activated murine peritoneal macrophage killed in vitro fish (Cyprinus carpio) PHA-induced lymphoblasts. Addition of PHA and WGA to effector-target cell cultures did not potentiate the killing. This killing (xenolysis) was expressed by non-elicited and thioglycollate-elicited macrophages as well as by macrophages depleted of lymphocytes. It is suggested that mammalian macrophages have a xenolytic potential towards phylogenetically distant species which is analogous to the capacity of invertebrate phagocytes to destroy xenografts.
Animals↗
The cells involved in the immune response of fish: II. PHA-induced clonal proliferation of carp lymphocytes in soft agar culture.
Lymphocytes from peripheral blood of carp proliferate in a clonal culture in soft agar, in the presence of phytohemagglutinin, generating several morphologically distinct types of colonies. Cells from colonies developing on the surface of the agar (surface colonies) and cells from colonies developing within the agar (agar colonies) were studied. Several differences were found between cells from the two types of colonies with respect to morphology, ultrastructure and the distribution of cytoplasmic determinants antigenically related to serum immunoglobulin. Colonies were quantitated as a function of the number of cells seeded, in primary cultures of peripheral blood leukocytes and in secondary (replated) cultures of isolated surface colony cells. The numbers of surface colonies and agar colonies in the two systems were comparable. Preferential formation of surface over agar colonies was noted, and there was an initial concentration of cells (individual for each fish) which resulted in optimal colony growth. This method was found to be suitable for isolating highly homogeneous subpopulations of PHA-responsive lymphocytes, which could subsequently be further expanded in liquid culture. A requirement for an exogenously produced growth factor (possibly similar to mammalian Interleukin 2) in the maintenance of long-term clonal cultures is suggested.
Agar↗
A new immunomodulating compound (AS-101) with potential therapeutic application.
There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer, but there are toxic effects resulting from the high doses of IL-2 required. We have developed a new synthetic compound, ammonium tri-chloro(dioxoethylene-O,O'-)tellurate (AS-101), which has immunomodulating properties and minimal toxicity. The effects of AS-101 on the activation and function of immunocompetent cells have been assessed. We have found that AS-101 induces proliferation and IL-2 production by human lymphocytes in vitro, and enhances the production of IL-2 and colony-stimulating factor by mouse spleen cells. Splenocytes of BALB/c mice injected with AS-101 increased production of IL-2 and CSF in vitro in the presence of mitogen. Mononuclear cells of normal donors acquired responsiveness to recombinant IL-2 and bound monoclonal antibody to IL-2 receptor after incubation with AS-101. Splenocytes of mice treated in vivo with AS-101 expressed high levels of IL-2 receptor. The stimulation of lymphocytes by AS-101 apparently involves an increase in intracellular free calcium. AS-101 administered systemically to mice mediated antitumour effects which could be attributable to its immunomodulatory properties. In addition, AS-101 could directly enhance the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS (acquired immune deficiency syndrome) patients. These results indicate that AS-101 is potentially useful in the treatment of clinical conditions involving immunosuppression.
Adjuvants, Immunologic↗
Immunogenetic aspects of clinical and experimental uveitis.
Genetic association of some immune-mediated human uveitic diseases with histocompatibility antigens, ethnic origin, familial background, or gender have suggested the presence a hereditary component in susceptibility. Experimental autoimmune uveoretinitis (EAU) can be induced in inbred rodents by immunization with evolutionarily conserved retinal proteins, and mimics many features of human uveitis. Susceptibility to EAU is genetically controlled, and the model is being used to study mechanisms that might affect susceptibility to ocular autoimmune disease. EAU expression in mice and in rats requires the presence of both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility in H-2k mice was tentatively mapped to the I-A subregion (HLA-DR equivalent), implicating epitope recognition as a major mechanism in susceptibility. In contrast, expression of the I-Ek gene product (HLA-DQ equivalent) appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include regulation of responses to lymphokines, hypothalamic-adrenal-pituitary axis hormones, mast cell/vascular effects, and possibly the T cell repertoire. The data are interpreted to suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background. These results might help to explain why only a minority of individuals with a susceptible HLA type develop uveitis, as well as the variable incidence of disease in HLA-identical populations of different ethnic backgrounds.
Animals↗