Alterations in spleen norepinephrine and lymphocyte [3H]dihydroalprenolol binding site number in genetically epilepsy-prone rats.

Noradrenergic neurotransmission plays an important role in normal immune reactivity. Genetically epilepsy-prone (GEPR-9) rats exhibit deficits in central noradrenergic systems and diminished plaque-forming cell responses following immunization in vivo. In the present study we examined the hypothesis that immunosuppression in GEPR-9 rats is associated with alterations in the splenic noradrenergic system. The content of norepinephrine (NE) in spleens of GEPR-9 age-matched nonepileptic Sprague-Dawley control rats was determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC). In addition, we measured the number of beta-adrenergic receptors on splenic lymphocyte membranes of GEPR-9 and control rats using the beta-adrenergic receptor antagonist dihydroalprenolol ([3H]DHA). HPLC-EC analysis revealed that splenic norepinephrine content was significantly greater in GEPR-9 rats than in controls. Results from receptor binding studies indicated a 33% reduction in specific binding of [3H]DHA to splenic lymphocyte membranes of GEPR-9 rats. Saturation of binding studies revealed a significant decrease in the maximum number of [3H]DHA binding sites on splenic lymphocyte membranes from GEPR-9 rats. These results indicate that the noradrenergic system in GEPR-9 rat spleen is altered. Whether either or both of these changes contribute to reduced immune reactivity in GEPR-9 rats remains to be determined.

Evidence of altered T-lymphocyte number and proliferative responses in genetically epilepsy-prone rats.

Genetically epilepsy-prone (GEPR-9) rats exhibit decreased antibody plaque-forming cell responses following immunization. We examined the hypothesis that this immunosuppression was due to deficits in the number or proliferative responses of T-lymphocytes. Splenocyte responses to concanavalin A and pokeweed mitogen were significantly greater in GEPR-9 rats than controls. Flow cytometric analysis indicated that GEPR-9 rats possess an increase in T-cells associated with the T-helper phenotype. The increased proportion of T-helper cells in GEPR-9 rats may underlie their enhanced proliferative responses to T-cell mitogens. These results clearly indicate that the failure of the GEPR-9 rat to respond to a T-dependent antigen in vivo is not due to a lack of T-helper activity.