Deuterium isotope effects on lymphoid tissues and humoral antibody responses in mice

Summary

Hematological and other morphological changes following body deuteration were evaluated in young adult pathogen-free female Swiss albino mice given heavy water (99.8% D₂O) as drinking fluid. Control groups included mice given tap water ad libitum, distilled water, or amounts of tap water equivalent to the reduced fluid intake of animals drinking D₂O. Deuterated mice manifested changes in their spontaneous activity, weight loss, fall in body temperature, atactic gait, ruffled fur, decrease in breathing rate and preterminal cachexia. The mice were killed in a moribund state after exposure to D₂O for about 2 weeks. At the time of death, packed red blood cell volumes were within normal range. Mean erythrocyte counts were not markedly reduced. In contrast, there was a conspicuous blood lymphocytopenia. The bone marrow displayed a normal cellularity and a moderate reduction in the proportion of erythropoietic cells. A particularly striking weight loss of thymus and spleen, and a marked systemic lymphocyte depletion were apparent, particularly in the thymus, white pulp of the spleen, lymph nodes, and gut-associated lymphoid tissue. Signs of increased cell death were found in lymphoid organs. The number of mitotic figures in intestinal cryt epithelia was reduced. Since D₂O is known to interfere with DNA synthesis and mitosis, the deuterium-induced systemic lymphocyte depletion was probably due to disturbed cell proliferation and increased cell death.

On the basis of these data, the effects of reduced levels of deuteration on antibody production and thymic morphology were also evaluated. Adult female Swiss albino mice, raised under specific pathogen-free conditions, were given drinking fluids composed of 10%, 20% and 40% D₂O during the experimental test period. After 7 days exposure, all animals were given a primary subcutaneous injection of tetanus toxoid, followed by a booster injection 49 days after primary stimulation. All animals were killed 7 days after the booster. Deuteration resulted in a dose-dependent depression of specific antibody production. Primary antitoxin responses were more affected than secondary responses. A marked reduction of the thymic cortical area of deuterated mice was proportional to the dose of D₂O. Deuterium-induced immunosuppression is tentatively linked to a diminution of the total body lymphoid cell mass and suppression of the plasmocytoid cells involved in antibody synthesis.