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Guangpu Shi, Barbara P. Vistica, Lindsey F. Nugent, Eric F. Wawrousek, Igal Gery; Acquisition of Th1, Th17, or Treg Phenotypes Differs Among CD4 T Cells in Ocular Inflammation Triggered by Different TLR Ligands. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2279.
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Our previous study showed that TLR ligands are capable of triggering ocular inflammation by converting naïve antigen-specific CD4 T cells into pathogenic effector cells. The underlying mechanisms have not been clarified, however. The present study was aimed at investigating the phenotype acquisition by the activated precursor cells.
Naive CD4 cells from transgenic mice expressing hen egg lysozyme (HEL)-specific T cell receptor were adoptively transferred into recipient mice expressing HEL in their lens. Various TLR ligands were injected on the following day. Proliferation of the transferred cells was monitored by CFSE dilution and their differentiation was analyzed by intracellular flow cytometry. The levels of cytokines in recipient sera were measured using ELISA.
Treatment with the ligands triggered proliferation by both FoxP3+ and FoxP3- donor cells accumulating in the recipient spleen. The ocular inflammation level in LPS-treated recipients was remarkably higher than in recipients treated with peptidoglycan (PGN), poly (I:C), or CpG oligodeoxynucleotide and the mean ratios between donor FoxP3- and FoxP3+ were 21, 14, 13 and 15 respectively. The mean ratios between donor Th17 and Th1 cells were 2.0, 1.3, 0.28 and 0.29, respectively. Significant serum levels of IL-6, IL-12 and IL-23 were detected at 3 hr post TLR ligand injection only in LPS-treated recipients, whereas on day 3 post injection, increased serum IL-12 levels were found only in CpG-treated recipients.
Treatment with TLR ligands initiates processes that stimulate antigen specific naïve CD4 T cells to proliferate and to acquire Th1, Th17 or Treg phenotypes that are determined by the cytokine milieu created by the ligands. Treg cells are generated along with the T-effectors and the ratio between these populations affects the inflammation levels.
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