Reactivity and Phenotype of Mononuclear Leukocytes from Nongravid Heifers After In Vitro Exposure to 9,13-di-cis-Retinoic Acid

Abstract

The predominant isomer of retinoic acid in the plasma of dairy cows during the periparturient period is 9,13-di-cis-retinoic acid. Because retinoic acids influence the activity of cells in a variety of tissues, including the immune system, the potential for this isomer to modulate the bovine immune system during the periparturient period must be considered. The present study examined the in vitro effects of 9,13-di-cis-retinoic acid on the reactivity and phenotype of blood mononuclear leukocytes from nongravid Holstein heifers that were sensitized to antigens and that had naturally low plasma concentrations of 9,13-di-cis-retinoic acid. In this system, 9,13-di-cis-retinoic acid, approximating the highest plasma concentrations occurring in vivo during the periparturient period, had no effect on DNA synthesis, secretion of interleukin-2 or interferon-γ, or secretion of immunoglobulin by unstimulated cultures or cultures stimulated by mitogen (pokeweed mitogen) or antigen (ovalbumin). The composition of unstimulated and stimulated mononuclear leukocyte populations, based on percentages of specific cell types, was unaffected by 9,13-di-cis-retinoic acid at the physiologic concentration of 10–8M. 9,13-di-cis-Retinoic acid did not affect the actual number of cells in unstimulated cultures and cultures stimulated by antigen but did cause a moderate reduction in the number of cells, primarily CD4+ lymphocytes, in cultures stimulated by mitogen. Overall, these results suggest that the elevated concentration of 9,13-di-cis-retinoic acid in maternal plasma may have a negligible effect on the reactivity and phenotype of cells constituting the circulating mononuclear leukocyte population.