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AW Taylor, D Yee; Ocular Cytokines and Factors Deactivate Antigen Presenting Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2292.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The ocular microenvironment suppresses the induction of inflammatory immunity partially through the constitutive production of immunosuppressive cytokines and factors. The induction of inflammatory immunity requires the activation of antigen presenting cells (APC) that stimulate activation of Th1 cells. Several ocular cytokines and factors of the eye can modify APC function therefore, we examined their potential to deactivate APC. Methods: Adherent spleen cells from naive BALB/c mice were used as APC. They were treated for 24 hours with antigen and a combination of α-melanocyte stimulating hormone (α-MSH), calcitonin gene related peptide (CGRP), α-defensin-1, or ß-defensin-2. The antigens we used were ovalbumin (OVA), whole M. tuberculosis (Mtb), or the soluble products of Mtb. The APC were then assayed for their ability to stimulate IFN-γ production by antigen-specific Th1 cells. In addition, we evaluated whether there was suppression of Toll-like receptor (TLR) activation of the APC by assaying the effects of the cytokines and factors on endotoxin (TLR dependent) and IFN-γ (TLR independent) induced nitric oxide production by J744 macrophage cells. Results: We deactivated OVA pulsed APC (suppression of IFN-γ production by antigen-specific Th1 cells) by treatment with α-MSH and CGRP. Whole Mtb pulsed APC were deactivated by only α-MSH. In contrast, APC pulsed with soluble Mtb products were deactivated by α-MSH but only if ß-defensin was added to the cultures. In addition, we found that α-MSH and the defensins suppressed LPS but not IFN-γ induced nitric oxide production by macrophages. Conclusion: Both α-MSH and CGRP suppress APC activation of antigen specific Th1 cells; however, only α-MSH and ß-defensin could suppress any innate immunity promoting activation of Th1 cells. The results demonstrate that aqueous humor cytokines and factors, and thus, the immune privileged ocular microenvironment, suppress different pathways in APC that lead to antigen-specific stimulation of Th1 cells.
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