Cytokines/chemokines

Oral

cd28 Co-stimulation Negatively Regulates Differentiation of Human but Not Mouse th17 Cells

Friday, June 16
6:15 PM - 7:30 PM

Th17 cells are important for protection from extracellular bacterial and fungal pathogens as well as homeostasis of commensal microbes. However Th17 cells are best known for driving autoimmune diseases, and anti-IL-17 is now approved for therapy of psoriasis and ankylosing spondylitis. Generation of in vitro Th17 cells requires multiple inducing cytokines, and has been notoriously difficult for human T cells. CD28 is a critical costimulatory molecule for T-cell activation and is routinely added with anti-CD3 during Th17 differentiation. Our data found that CD28 co-stimulation suppressed Th17 cells in a dose-dependent manner, as detected by IL-17 and RORγt. Although activation of T cells with anti-CD3 alone resulted in very few CD45RO+ activated T cells, addition of Th17-inducing cytokines overcame the deficit. Preliminary results indicate that Th17 cells generated in absence of CD28 are not anergic and maintain their Th17 phenotype. We are also investigating molecular mechanisms by which CD28 suppressed Th17 differentiation in human T cells. In contrast to human, addition of anti-CD28 to mouse Th17 cultures resulted in enhanced responses, fitting with known differences in CD28 costimulation effects between mouse and human. Together, these data provide new insight into mechanisms that regulate the generation of human Th17 cells, and have implications for approaches to target Th17 cells in autoimmune disease.

Shankar Kumar Revu

Post doctoral associate
University of Pittsburgh

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    Jing Wu

    Post doctoral associate
    University of Pittsburgh

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      Matthew Henkel

      Medical Lab technician
      University of Pittsburgh

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        Gerard Hernandez

        Graduate student
        University of Pittsburgh

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          Mandy McGeachy

          Assistant Professor
          University of Pittsburgh

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