JUN 26, 2017 08:00 AM PDT

WEBINAR: Finding pathologic T cells in rheumatoid arthritis by mass cytometry

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  • Rheumatologist Co-Director, Human Immunology Center Brigham and Women's Hospital Boston, MA
      Dr. Deepak Rao, MD, PhD, is an instructor in medicine and Co-Director of the Human Immunology Center at Brigham and Women's Hospital in Boston, MA. After completing undergraduate studies at Harvard University, he obtained an MD and a PhD in immunobiology from Yale University School of Medicine, where he studied human T cell responses to transplanted organs in the laboratory of Dr. Jordan Pober. He then completed internal medicine residency and rheumatology fellowship training at Brigham and Women's Hospital. During this time, he received the 2014 American College of Rheumatology Distinguished Fellow Award and the 2016 Rheumatology Research Foundation Malawista Endowment Designation for his research characterizing lymphocyte abnormalities in patients with rheumatic diseases. His work employs high-dimensional and functional analyses of T cells in blood and tissue samples from patients with rheumatoid arthritis, lupus and other rheumatic diseases.
    • Field Applications Scientist, Fluidigm
        Michelle Poulin earned her B.A. from Smith College and her Ph.D. in Immunology from the University of Colorado Denver. After completing a post-doctoral fellowship at National Jewish Health in 2003, Michelle joined BD Biosciences as an instructor in the Customer Education department. In 2012, Michelle joined DVS Sciences as a field applications scientist (FAS) and became manager of the North American FAS team shortly after DVS was acquired by Fluidigm in 2014.


      Unfortunately due to technical issues this webinar has been delayed until June 26th. If you are unable to make the new time, it will be available on demand for you to view.

      DATE: June 26, 2017
      TIME: 8:00AM PDT 11:00AM EDT

      Determining the pathologic functions of T cells that infiltrate target tissues remains a central challenge in autoimmune diseases. In this webinar, Dr. Deepak Rao, MD, PhD, of Brigham and Women’s Hospital will describe recent work, published in Nature, identifying a unique population of pathologic CD4+ T cells, called T peripheral helper (TPH) cells, that is markedly expanded in the joints of subjects with rheumatoid arthritis (RA). Rao and colleagues used mass cytometry and multidimensional flow cytometry to interrogate T cell populations in synovial tissue and blood from research subjects with RA, a chronic immune-mediated arthritis that affects up to 1% of the population.

      Mass cytometric analysis of RA synovial tissue cells revealed a strikingly expanded population of PD-1hiCXCR5-CD4+ T cells, which constituted ~25% of synovial CD4+ T cells. Surprisingly, these cells are not exhausted, but instead highly express factors that confer the ability to help B cells, including IL-21, CXCL13, ICOS, SAP and MAF. Like T follicular helper (TFH) cells, PD-1hiCXCR5- cells from synovium and blood induce plasma cell differentiation in vitro via IL 21. However, RNA-seq transcriptomics robustly separates PD-1hiCXCR5- cells from TFH cells, with altered expression of Bcl6 and Blimp-1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1 and CCR5, in PD-1hiCXCR5- cells.
      Rao and colleagues propose that PD-1hiCXCR5- T cells represent a TPH cell population, analogous to TFH cells, that supports B cell responses in pathologically inflamed nonlymphoid tissues. Given their marked expansion in RA joints, these cells may be important in driving pathologic B cell responses and autoantibody production within the inflamed target tissue.

      Michelle Poulin, PhD, of Fluidigm will give a brief overview of mass cytometry, the high-parameter, single-cell analysis technology used by Rao in his research.

      Learning Objectives:

        • Which activation markers can be used to identify populations of activated CD4+ T cells?

        • How can multiple methodologies such as mass cytometry, transcriptomics and functional assays be used in              concert to define immune cell subsets?

        • How might certain T cell subsets promote B cell responses within inflamed tissues?

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