May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Reciprocal Interactions Between T Cells and RPE Cells Lead to Alterations in T Cell Activation
Author Affiliations & Notes
  • D.S. Gregerson
    Ophthalmology, University of Minnesota, Minneapolis, MN
  • K.L. Lew
    Ophthalmology, University of Minnesota, Minneapolis, MN
  • T. Tran
    Ophthalmology, University of Minnesota, Minneapolis, MN
  • N.D. Heuss
    Ophthalmology, University of Minnesota, Minneapolis, MN
  • S.W. McPherson
    Ophthalmology, University of Minnesota, Minneapolis, MN
  • D.A. Ferrington
    Ophthalmology, University of Minnesota, Minneapolis, MN
  • Footnotes
    Commercial Relationships  D.S. Gregerson, None; K.L. Lew, None; T. Tran, None; N.D. Heuss, None; S.W. McPherson, None; D.A. Ferrington, None.
  • Footnotes
    Support  NIH Grant R01 EY11542, NIH Core Grant P30 EY11374, Research to Prevent Blindness, the Anna Heilmaier Foundation, and the MN Lions
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5141. doi:
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      D.S. Gregerson, K.L. Lew, T. Tran, N.D. Heuss, S.W. McPherson, D.A. Ferrington; Reciprocal Interactions Between T Cells and RPE Cells Lead to Alterations in T Cell Activation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5141.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : RPE have been reported to influence T cell responses through a variety of mechanisms that include soluble factors and cell–cell contact. Details of several of these interactions have been elusive. We have examined the outcomes of attempts to activate naive CD4 T cells with specific antigen by RPE that have been induced to express MHC class II, and by splenic APC in the presence of an RPE monolayer.

Methods: : HPV E6/E7 immortalized, syngeneic murine RPE were cultured with IFN–g and TNF–a to upregulate MHC class II, and then included in cultures with naive, antigen–specific CD4 T cells in the presence or absence of "professional" APC and specific antigen. The T cells were collected from TCR–transgenic mice with specificity for beta–galactosidase. Cultures were harvested after 2 to 5 days. The RPE and T cells were assessed by flow cytometry for cell–associated indicators of activation. Supernatants were taken for cytokine ELISAs.

Results: : T cells incubated with antigen in the presence of cytokine–treated RPE upregulated expression of CD25, CD69, and CD44, but failed to proliferate and did not produce IL–2, IL–4, IFN–g, or TNF–a. An antigenic peptide corresponding to the appropriate epitope of beta–galactosidase was capable of providing TCR occupancy, probably by loading directly into cell surface class II, while intact protein antigen was not. Since the RPE cells expressed B7 and B7–H1, several strategies were taken to further provide exogenous "second signal" or block regulatory B7 family members. None of these restored T cell responsiveness, suggesting that B7–like molecules do not participate in the inhibitory mechanism. Although CD25 was substantially upregulated, addition of exogenous IL–2 did not support T cell proliferation. The regulatory activity was dominant, since the RPE also inhibited T cell activation if APC were added. The viability of the T cells in the presence of RPE was strikingly elevated relative to T cells cultured with or without conventional APC. There was no evidence for FasL–mediated induction of apoptosis in the T cells.

Conclusions: : RPE are well–placed to moderate the antigen–specific activation of T cells in conditions whereby pro–inflammatory molecules have upregulated MHC on the RPE cells. Our data suggests that under these conditions, RPE could directly present degraded peptide fragments through MHC class II to T cells, aborting their effector capabilities.

Keywords: immunomodulation/immunoregulation • immune tolerance/privilege • retinal pigment epithelium 

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