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.
Green-Johnson
J M
JM
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Zalcman
S
S
Vriend
C Y
CY
Nance
D M
DM
Greenberg
A H
AH
D000818:Animals; D002524:Cerebellar Ataxia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000502:physiology*; D009479:Neuropeptides / Q000032:analysis; D009638:Norepinephrine / Q000032:analysis*; D013154:Spleen / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D007075:Immunoglobulin M; D009479:Neuropeptides; D003345:Corticosterone; D009638:Norepinephrine