Dopamine beta-hydroxylase deficiency impairs cellular immunity

Norepinephrine, released from sympathetic neurons, and epinephrine, release d from the adrenal medulla, participate in a number of physiological proces ses including those that facilitate adaptation to stressful conditions. The thymus, spleen, and lymph nodes are richly innervated by the sympathetic n ervous system, and catecholamines are thought to modulate the immune respon se. However, the importance of this modulatory role in vivo remains uncerta in. We addressed this question genetically by using mice that lack dopamine beta-hydroxylase (dbh(-/-) mice), dbh(-/-) mice cannot produce norepinephr ine or epinephrine, but produce dopamine instead. When housed in specific p athogen-free conditions, dbh(-/-) mice had normal numbers of blood leukocyt es, and normal T and B cell development and in vitro function. However, whe n challenged in vivo by infection with the intracellular pathogens Listeria monocytogenes or Mycobacterium tuberculosis, dbh(-/-) mice were more susce ptible to infection, exhibited extreme thymic involution, and had impaired T cell function, including Th1 cytokine production. When immunized with tri nitrophenyl-keyhole limpet hemocyanin, dbh(-/-) mice produced less Th1 cyto kine-dependent-IgG2a antitrinitrophenyl antibody. These results indicate th at physiological catecholamine production is not required for normal develo pment of the immune system, but plays an important role in the modulation o f T cell-mediated immunity to infection and immunization.