T peripheral helper cells in autoimmune diseases*

Abstract

Pathologic T cell-B cell interactions underlie many autoimmune diseases. The T cells that help B cells in autoimmune diseases vary in phenotype and include T cells that lack typical features of T follicular helper cells, such as expression of CXCR5 and BCL6. A population of PD-1 hi CXCR5 -T peripheral helper (Tph) cells has now been recognized in multiple autoantibody-associated diseases. Tph cells display a distinctive set of features, merging the ability to provide B cell help with the capacity to migrate to inflamed peripheral tissues. Here, we review the scope of immune-related conditions in which Tph cells have been implicated and provide a perspective on their potential contributions to pathologic B cell activation in autoimmune diseases. We discuss Tph cells as a promising therapeutic strategy in autoimmunity and consider the utility of tracking Tph cells in blood as a biomarker to quantify aberrant T cell-B cell activation in patients with autoimmune diseases.

Longitudinal Immune Cell Profiling in Patients With Early Systemic Lupus Erythematosus

“…Although we envision alterations in these cell phenotypes as potential metrics for identifying immune activation in patients being evaluated for a diagnosis of SLE, increases in levels of Tph cells, Tfh cells, ABCs, and plasmablasts have been observed in the setting of several diseases, such as RA, Sjögren's syndrome, and systemic sclerosis (35)(36)(37)(38)(39). While cellular changes are particularly pronounced in SLE, it seems unlikely that an increase in the levels of these cell populations will provide a specific diagnostic test for SLE; rather, the levels of these cell populations may provide a measurement of disease activity-reflecting the typical changes seen in active SLE-even though these changes may also occur in other diseases.…”

Co-Inhibitory Molecules – Their Role in Health and Autoimmunity; Highlighted by Immune Related Adverse Events

“…The increased expression correlates with disease activity, probably representing an immune activation. Looking further into the cellular and peripheral populations, PD-1 expression is associated with a pathological T cell phenotype involved in B cell activation and plasma cell maturation, resulting in increased antibody production and disease severity ( 58 , 59 ). However, PD-1 expression also characterize regulatory T cells (Treg) and Tex which both are associated with less immune activation, and a better prognosis in autoimmune diseases ( 32 , 57 ).…”

Many Achilles’ heels of B and T cell tolerance

“…The discovery and characterization of Tph cells-reviewed in this issue by Marks and Rao-represents an extremely elegant example of basic discovery that starts with patients. 16 Rao and colleagues initially identified a population of T cells with high PD-1 expression but lacking CXCR5 that is remarkably and uniquely enriched in the joints of patients with seropositive (but not seronegative) rheumatoid arthritis (RA). They went on to show that these cells, also detectable in peripheral blood, express a transcriptional program and harbor functional features of B cell helper cells with the capacity to secrete IL-21 and promote B cell differentiation; they are therefore much like Tfh cells but are localized outside of secondary lymphoid organ germinal centers and instead home to peripheral sites.…”

“…The discovery and characterization of Tph cells—reviewed in this issue by Marks and Rao—represents an extremely elegant example of basic discovery that starts with patients 16 . Rao and colleagues initially identified a population of T cells with high PD‐1 expression but lacking CXCR5 that is remarkably and uniquely enriched in the joints of patients with seropositive (but not seronegative) rheumatoid arthritis (RA).…”