March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Cell-cell Interaction with APC, not IL-23, is Required for Naive CD4 Cells to Acquire Pathogenicity During Th17 Lineage Commitment
Author Affiliations & Notes
  • Guangpu Shi
    National Eye Institute, Bethesda, Maryland
  • Jenna D. Lovaas
    National Eye Institute, Bethesda, Maryland
  • Cuiyan Tan
    National Eye Institute, Bethesda, Maryland
  • Barbara P. Vistica
    National Eye Institute, Bethesda, Maryland
  • Eric F. Wawrousek
    National Eye Institute, Bethesda, Maryland
  • Mehak K. Aziz
    National Eye Institute, Bethesda, Maryland
  • Rachael C. Rigden
    National Eye Institute, Bethesda, Maryland
  • Rachel R. Caspi
    National Eye Institute, Bethesda, Maryland
  • Igal Gery
    National Eye Institute, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  Guangpu Shi, None; Jenna D. Lovaas, None; Cuiyan Tan, None; Barbara P. Vistica, None; Eric F. Wawrousek, None; Mehak K. Aziz, None; Rachael C. Rigden, None; Rachel R. Caspi, None; Igal Gery, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5487. doi:https://doi.org/
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      Guangpu Shi, Jenna D. Lovaas, Cuiyan Tan, Barbara P. Vistica, Eric F. Wawrousek, Mehak K. Aziz, Rachael C. Rigden, Rachel R. Caspi, Igal Gery; Cell-cell Interaction with APC, not IL-23, is Required for Naive CD4 Cells to Acquire Pathogenicity During Th17 Lineage Commitment. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5487. doi: https://doi.org/.

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

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Abstract

Purpose: : Pathogenic or nonpathogenic Th17 cells have been reported to develop when pre-sensitized CD4 cells were polarized by either IL-23 or IL-6/TGF-β, respectively, during activation with their target antigen (McGeachy et al, Nat. Immunol.,2007). We reported, however, that naïve CD4 cells differentiate into pathogenic Th17 when polarized with IL-6/TGF-β during activation with their antigen, without IL-23 (Shi et al. J. Immunol.2009). The present study was aimed at investigating the acquisition of pathogenicity by Th17 generated from naïve CD4 cells.

Methods: : Naïve CD4 cells from TCR transgenic mice specific to hen egg lysozyme (HEL) were polarized with IL-6/TGF-β and, concurrently, were activated either with HEL presented by APC ("HEL/APC"), or with plate-bound anti-CD3/CD28 Abs ("PbAb"). Pathogenicity was assessed by the capacity of Th17 cells to induce inflammation in eyes of recipient mice expressing HEL in their lens.

Results: : HEL/APC Th17, but not PbAb Th17, induced inflammation in the recipients’ eyes. Unlike with pre-sensitized Th17, soluble IL-23 does not participate in pathogenicity acquisition by naïve CD4 cells: no pathogenicity was induced by adding IL-23 to cultures generating PbAb Th17. Furthermore, Abs against IL-23 or IL-23R did not inhibit acquisition of pathogenicity in cultures generating HEL/APC Th17. PbAb Th17 acquired pathogenicity, however, when co-cultured with HEL/APC. Importantly, the naïve CD4 cells did not acquire pathogenicity when co-cultured with activated APC alone, or when separated from the HEL presenting cells by a semi-permeable membrane.

Conclusions: : Unlike pre-sensitized CD4 cells, naïve CD4 polarized toward Th17 phenotype acquire pathogenicity only by direct interaction with APC presenting the Ag, with no apparent involvement of soluble IL-23. We suggest that the Th17 lymphocytes derived from naive CD4 cells participate in pathogenic and other immune processes, along with the IL-23 dependent Th17 cells.

Keywords: inflammation • cell-cell communication • immunomodulation/immunoregulation 
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