REACTIVITY AND PHENOTYPE OF MONONUCLEAR LEUKOCYTES FROM NONGRAVID HEIFERS AFTER IN-VITRO EXPOSURE TO 9,13-DI-CIS-RETINOIC ACID

The predominant isomer of retinoic acid in the plasma of dairy cows du ring the periparturient period is 9,13-di-cis-retinoic acid. Because r etinoic acids influence the activity of cells in a variety of tissues, including the immune system, the potential for this isomer to modulat e the bovine immune system during the periparturient period must be co nsidered. The present study examined the in vitro effects of 9,13-di-c is-retinoic acid on the reactivity and phenotype of blood mononuclear leukocytes from nongravid Holstein heifers that were sensitized to ant igens and that had naturally low plasma concentrations of 9,13-di-cis- retinoic acid. In this system, 9,13-di-cis-retinoic acid, approximatin g the highest plasma concentrations occurring in vivo during the perip arturient period, had no effect on DNA synthesis, secretion of interle ukin-2 or interferon-gamma, or secretion of immunoglobulin by unstimul ated cultures or cultures stimulated by mitogen (pokeweed mitogen) or anti gen (ovalbumin). The composition of unstimulated and stimulated m ononuclear leukocyte populations, based on percentages of specific cel l types, was unaffected by 9,13-di-cis-retinoic acid at the physiologi c concentration of 10(-8) M. 9,13-di-cis-Retinoic acid did not affect the actual number of cells in unstimulated cultures and cultures stimu lated by antigen but did cause a moderate reduction in the number of c ells, primarily CD4(+) lymphocytes, in cultures stimulated by mitogen. Overall, these results suggest that the elevated concentration of 9,1 3-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.