Rao and Poulin Finding pathologic T cells in rheumatoid arthritis by mass cytometry

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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.