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Deming Sun, Hong Nian, IV, Hanry J. Kaplan, Hui Shao; Enhancing And Inhibitory Effects Of T Cells On Uveitogenic αβ T Cells Are Convertible. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3394.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the role of γΔ T cells in the pathogenesis of EAU and in the generation of uveitogenic T cells and determine whether γΔ T cell subsets have different effects on Th1 and Th17 autoreactive T cells
Purified γΔ T cells were isolated from immunized B6 or transgenic mice expressing V γ1TCR, using MACS column. γΔ T cell-free responder (αβ T) cells were obtained from TCR-Δ -/- mice immunized with the uveitogenic peptide (IRBP1-20). The intensity of autoreactive T cell response was assessed by T cell proliferation, cytokine production and intracellular staining (ICS) of cytokine expression. Differentiation of uveitogenic T cell under Th1 (addition of IL-12 and anti-IL-4 antibody) or Th17 polarized (addition of IL-23) conditions was also determined. Adoptive transfer of activated IRBP-specific T cells to naïve mice was performed to assess whether the autoreactive T cells gained increased or decreased pathogenic activities when activated with or without the tested γΔ T cells
i) relative abundance of γΔ and αβ T cells switched the enhancing and inhibitory effect of γΔ cells - while a modest increase of γΔ T cells (1-5% of the total T cells) enhanced the response of αβ autoreactive T cell, a higher percentage of γΔ T cells (>10% of the total T cells) suppressed the response of αβ T cells; ii) activation of γΔ T cells converted their regulatory function from suppression to enhancement - activated γΔ T cells enhanced the response, whereas non-activated γΔ T cells suppressed the response; and iii) γΔ T cells had a stronger regulatory effect on Th17- than Th1-type of uveitogenic T cells.
i) γΔ T cells are actively involved in the generation of uveitogenic T cells in EAU; ii) functional diversity is contributed by the activation status of γΔ T cell, iii) enhancing and inhibitory effects of a specific γΔ T cell subset is convertible and regulated by environmental factors
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