Low Dose HIV-1 Tat Improves the Defective Nuclear Factor (NF)-kappaB Activity of Dendritic Cells from Persons with Spinal Cord Injury

Deficits of immune function may be involved in the infections associated with spinal cord injury (SCI). Previous report showed that the impaired maturation potential of dendritic cells (DCs) contributes to immune defect in persons with SCI, especially in those with tetraplegia. To evaluate the roles of cell signaling in the impaired maturation potential of DCs, we assessed the phenotypic and functional maturation potential of DCs in 20 subjects with trauma-induced stable SCI and their neurologically intact healthy control in the presence of DC stimulators, including HIV-1 Tat protein (Tat). Our results showed the tetraplegic subjects had an impaired maturation potential of DCs. The impairment could be attributed to insufficient nuclear factor (NF)-kappaB activity. The maturation potentials and NF-kappaB activity of DCs in response to stimulators could be improved by pretreatment with Tat, although Tat did not increase DC maturation. The improvement by Tat pretreatment was inhibited by a specific NF-kappaB blocker. We concluded that HIV-1 Tat could improve the maturation potentials of DCs from tetraplegic subjects, through Tat-induced enhancement of NF-kappaB activity. These data suggest a potential therapeutic role of HIV-1 Tat in improving immune function in tetraplegic persons.