Peripheral Helper Cells May Provide Clue to RA Pathology

T_PH cells are also unique in that they express chemokine receptors, such as CCR2, CXCR1 and CCR5, which direct migration to inflamed sites. Thus, the newly identified T cell population is able to infiltrate parts of the body that are inflamed and stimulate B cells to produce antibodies. In particular, the investigators found that PD-1^hiCXCR5^–CD4⁺ T cells that had been sorted from the synovial tissue or fluid of patients with RA could induce differentiation of co-cultured memory B cells into plasma cells. In contrast, CXCR5^– cells that did not have high PD-1 expression could not stimulate a B cell response.

The fact that T_PH cells are uniquely enriched in seropositive RA implies that they are critical for the T cell-B cell interactions that are characteristic of seropositive disease. “Our results help illuminate a path toward treatment that is much more precise and focused only on the most relevant immune cells,” said Dr. Rao in a press release.

To that end, the investigators intend to focus their future research on developing a better understanding of the signals required to develop T_PH cells, as well as the role these cells may play in other autoimmune diseases. Such studies may reveal whether the presence of T_PH cells may be a useful diagnostic biomarker or, alternatively, a predictive biomarker that can be used to identify which patients are most likely to respond to therapies, such as rituximab, that directly target T cell-B cell interactions.

“This work is a remarkable illustration of the power of our disease deconstruction approach,” says senior author Michael B. Brenner, MD, who also directs BWH’s Human Immunology Center with Dr. Rao, in a press release. “We hope it will prove equally illuminating as we apply it to other immune-mediated diseases.”

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference

1. Rao DA, Gurish MF, Marshall JL, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017 Feb 1;542(7639):110–114. doi: 10.1038/nature20810.