SUPPRESSED T-CELL AND MACROPHAGE FUNCTION IN THE REELER (RL/RL) MUTANT, A MURINE STRAIN WITH ELEVATED CEREBELLAR NOREPINEPHRINE CONCENTRATION

The effects of neurochemical alterations in specific brain regions on the immune system were examined in reeler (rl/rl) mice, a neurologic mutant strain having an abnormally high concentration of cerebellar norepinephrine (NE). Following immunization with sheep red blood cells, lower numbers of IgM-producing B cells were found in rl/rl mice than in B6C3Fea/a controls. Interleukin-1 (IL-1) production by splenic macrophages from rl/rl mice was reduced compared to B6C3F3a/a controls, as was the proliferative response of splenic T lymphocytes from rl/rl mice activated with an anti-CD3 monoclonal antibody. Levels of IL-4, interferon-gamma and IL-2 produced by splenic T lymphocytes from rl/rl mice were also lower than those of B6C3Fea/a controls. Rl/rl mice do not have an intrinsic defect in the ability to produce IgM, as lipopolysaccharide activated splenic lymphocytes from rl/rl mice produced levels of IgM similar to those of controls. This suggests that defective function in the T lymphocyte and/or macrophage population rather than in the B cell population may underlie the defect in IgM production. No significant alterations were observed in basal splenic levels of NE or neuropeptides in rl/rl mice relative to controls. The reeler mouse model shows that alterations in immune function are present in a strain with inherited alterations in cerebellar noradrenergic innervation and NE concentration. (C) 1995 Academic Press, Inc.