Red Blood Cell Immunization Research Articles

Investigation into the immunological effects of miltefosine, a new anticancer agent under development

Miltefosine is the prototype of alkylphosphocholines, a new class of anticancer agents related to alkyl-lysophospholipids. These agents were considered to possess potent immunomodulatory properties. Miltefosine was highly active against the human KB tumour xenograft in nude mice, leading to growth inhibition as well as regression of large established tumours, which suggested that its mode of action was not mediated by the T cell system. In vivo natural killer cell activity was measured by chromium release of YAC-1 cells using spleen cells from treated animals as effector cells. Miltefosine had no significant effect on YAC-1 cytolysis. Similarly, the compound did not induce cytotoxic spleen cells against KB target cells. The results were identical when spleen cells from tumour-bearing animals were used. Humoral antibody production in rats following sheep red blood cell immunization was not changed by miltefosine pretreatment. Finally, the in vitro phagocytic activity of mouse bone marrow macrophages was not stimulated but rather inhibited in a dose-dependent manner. In conclusion, there is no experimental evidence that the miltefosine action is mediated by the host immune system and no major immunotoxicity was observed.

Stereospecific Effects of (–)- and (+)-7-Hydroxy-Delta-6-Tetrahydrocannabinol-Dimethylheptyl on the Immune System of Mice

The effects of the (+) and (-) cannabinoid enantiomers 7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl [(-)-7-OH-delta-6-THC-DMH (HU-210) and (+)-7-OH-delta-6-THC-DMH (HU-211)] on the inductive and productive phases of the primary humoral immune response to sheep red blood cell immunization were investigated in mice. Animals treated with (-)-7-OH-delta-6-THC-DMH (0.01, 0.05, 0.1 and 0.5 mg/kg) exhibited a dose-dependent suppression of both phases of the primary humoral immune response in the hemolytic plaque assay, the hemagglutination titer and in the ratio of the spleen weight to final body weight. Mice treated with (+)-7-OH-delta-6-THC-DMH (0.01, 0.05, 0.01, 0.5 and 1.0 mg/kg) did not exhibit dose-dependent immune suppression. However, the (+) enantiomer reduced the number of plaque-forming cells in the hemolytic plaque assay during the inductive phase. Mice treated with a combination of (-) and (+) enantiomers, each at 0.01 mg/kg, exhibited no impairment in ability to undergo a primary humoral immune response (inductive phase).

Immunopathology of chronic cadmium administration in mice

Young male mice were given drinking water containing 50 ppm cadmium (Cd) for 3 weeks, and were killed 0, 3 and 6 weeks after the cessation of treatment. At 0 weeks, suppression in the number of splenic plaque-forming cells in response to sheep red blood cell immunization was noted 5 days after antigen injection, but not 7 days after injection. Plasma IgG concentration and thymic factor activity were unaffected at 0 weeks. The number of circulating lymphocytes tended to be less in the Cd-treated mice at all times. Cd treatment had no effect upon liver and kidney weights, and upon the weights and the lymphocyte contents of the thymus and spleen at any of the observation times. Employing immunofluorescence with anti-mouse IgG and C3, no evidence of an autoimmune response was found in the kidneys of the treated mice at 0 and 3 weeks. Mitochondrial abnormalities in the renal proximal tubule cells were noted at 0 weeks in the Cd-treated mice. The Cd concentrations of the liver and kidneys remained high at all observation times. The results suggest that a modest dose of Cd produces some depression of the immune system, and the biological half-life of Cd is long.

Characterization of mixed allogeneic chimeras. Immunocompetence, in vitro reactivity, and genetic specificity of tolerance.

Mixed allogeneically reconstituted mice (B10 + B10.D2----B10) that specifically accept B10.D2 tail skin allografts were examined for in vivo and in vitro immunocompetence, patterns of hematopoietic repopulation, and in vitro reactivity. In vitro, mixed allogeneic chimeras (B10 + B10.D2----B10) manifested specific tolerance in mixed lymphocyte reactions and cell-mediated lympholysis to B10 and B10.D2 splenocytes, with normal responses to third-party (B10.BR) cells. Such chimeras were immunocompetent in B cell and helper T cell responses, as assessed by their primary plaque forming cell responses to in vivo sheep red blood cell immunization. This is in contrast to fully allogeneic chimeras, which responded less well. In addition, survival of the mixed allogeneic chimeras in a conventional animal facility was superior to that of fully allogeneic chimeras, and similar to syngeneically reconstituted (B10----B10) mice. Specific tolerance to skin grafts, degree of allogeneic engraftment, and persistence of chimerism was also assessed in a noncongenic mixed allogeneic combination (B10 + C3H----B10). Such animals manifested specific hyporeactivity to C3H skin allografts, but eventual chronic rejection of the grafts occurred in spite of stable and persistent mixed chimerism. MHC-congenic (B10.BR) skin grafts were accepted indefinitely in the same animals, suggesting that skin-specific non-major histocompatibility complex antigens were responsible for rejection of the C3H skin allografts.

Effect of artemether on red blood cell immunity in murine malaria

Effect of artemether on red blood cell immunity in murine malaria

Immunoglobulin determinants on rosette-forming cells: their changing nature during an immune response.

SummaryAntisera to mouse immunoglobulin heavy and light chains were used in vitro to inhibit the formation of rosettes in mouse spleen cell suspensions taken at intervals after sheep red blood cell immunization. Anti‐kappa produced greater than 90% inhibition of both immune and non‐immune rosettes. 65–80% inhibition of non‐immune and immune rosettes was induced by anti‐μ, up to 14 days after injection. Late in the response anti‐μ inhibited rosettes by less than 50%. Anti‐γ inhibited immune rosettes only, increasing to 42% inhibition on the 28th day of response. Anti‐α inhibited rosette formation only during the peak of the response. These results are discussed as relating to antigen‐binding receptors on rosette‐forming cells.