CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells.

Considerable attention has been given to CCR6+ IL-17-secreting CD4+ T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6+ cells in MS CSF. Here we identify the dominant CCR6+ T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease.

DSP-4 treatment influences olfactory preferences of developing rats.

Control cagemates of rats treated with the norepinephrine (NE) neurotoxin DSP-4, showed normal olfactory learning as infants, but abnormal aversion to home-cage odors as juveniles. Neither age nor social housing conditions influenced the odor preferences of DSP-4-treated rats: they showed tolerance or attraction to familiar odors at both developmental stages. Controls, but not DSP-4-treated juveniles, housed in mixed treatment groups, showed elevated concentrations of a serotonin metabolite and reduced NE concentrations in the hippocampus, suggesting that this social situation was particularly stressful for the controls. DSP-4-treated juveniles, but not infants, produced odors that were discriminable from controls'. Thus, conflicting olfactory signals in the home-cages of mixed juvenile groups may have led to the development of stress in controls. NE depletion appeared to lessen social stress effects in their DSP-4-treated cagemates. These findings support other data suggesting that NE modulates the biobehavioral effects of the social environment.