IFN-γ secretion is polarized at effector immunological synapses (IS) in vivo. (87.52)

Abstract

Abstract In vitro cytokine secretion by T cells is polarized. For example, IFN-γ secretion is focused towards the immunological synapse (IS), while secretion of TNFα is multi-directional. Whether polarized cytokine secretion occurs in vivo is unknown. We studied the intracellular distribution of IFN-γ within T cells establishing IS with infected astrocytes in vivo. Astrocytes were infected with an adenovirus (Ads) expressing Thymidine Kinase (TK), a marker for infected cells. 30 days later we induced a systemic immune response against Ads, and 14 days after the immunization animals were sacrificed and brains studied by immunohistochemistry and confocal microscopy. Brain sections were stained for TCR, LFA-1, TK and IFN-γ. Confocal analysis revealed that IFN-γ is polarized in T cells establishing close anatomical contacts with Ad infected cells. Polarization was found in cells with or without polarized LFA-1 or TCR. This demonstrates that in vivo IFN-γ is selectively polarized towards the APC, and further suggests that maturation of the IS is not necessary for IFN-γ polarization. In consequence, polarized IFN-γ secretion may precede the maturation of immunological synapses. This work was funded by grants from NINDS, NIH.