Poster Sessions

Imm-26

Guangpu Shi

G. Shi, B. Vistica, M. Ramaswamy, C. Tan, E. Wawrousek, R. Siegel, I. Gery

UNLIKE TH1, TH17 CELLS MEDIATE SUSTAINED AUTOIMMUNE INFLAMMATION BY THEIR RELATIVE RESISTANCE TO RESTIMULATION-INDUCED CELL DEATH

To learn about immunopathogenic activities of Th1 and Th17 lineages, we used a system in which TCR-transgenic Th1 or Th17 induce ocular inflammation in recipient mice expressing the specific antigen in their eye. Th1 divided in recipient mice considerably faster than Th17 cells, as measured by CFSE dilution. Th1 also invaded the recipient eyes one day earlier than Th17 cells. After disease severity peak around day 5, inflammation in Th1 recipient eyes receded rapidly, but was sustained in Th17 recipient eyes throughout the 15 days testing period. Th17 remained the majority among eye infiltrating cells and their actual number even increased slightly during the observation period, while Th1 cell number declined following their peak and their proportion among infiltrating cells declined rapidly. Th17 were more resistant to restimulation-induced apoptosis, a major pathway whereby restimulated Th1 are eliminated. This resistance to apoptosis was due to compromised Fas-induced apoptosis pathway in Th17 relative to Th1 cells, despite normal expression of Fas. Moreover, Th1 express a higher level of FasL than Th17 cells. The overall expression level of FasL was also remarkably lower in Th17 than in Th1 recipient eyes, in accord with the relative resistance to apoptosis of Th17 cells.