Finding Pathologic T Cells in Rheumatoid Arthritis by Mass Cytometry

Researchers identify a unique population of pathologic CD4+ T cells

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Researchers identify a unique population of pathologic CD4+ T cells in both blood and synovial fluid using mass cytometry

In this video, Dr. Deepak Rao, MD, PhD, of Brigham and Women’s Hospital presents his recent research using mass cytometry and multidimensional flow cytometry to identify key pathologic T cell populations in the synovial fluid of subjects with rheumatoid arthritis.

Determining the pathologic functions of T cells that infiltrate target tissues remains a central challenge in autoimmune diseases. In this video, Dr. Deepak Rao, MD, PhD, of Brigham and Women’s Hospital describes 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 enabling B cell help, 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 provides a brief overview of mass cytometry, the high-parameter, single-cell analysis technology used by Rao in his research.

Speakers

Deepak Rao

Dr. Deepak Rao, MD, PhD   
Rheumatologist   
Co-Director, Human Immunology Center    
Brigham and Women's Hospital 
Boston, MA

Michelle Poulin

Michelle Poulin, PhD
Applications Scientist
Fluidigm Canada Inc. 
Markham, ON, Canada

fluidigm

For Research Use Only. Not for use in diagnostic procedures.