Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

Abstract

The interactions of CD4 + T cells and B cells are fundamental for the generation of protective antibody responses, as well as for the development of harmful autoimmune diseases. Recent studies of human tissues and blood samples have established a new subset of CD4 + B helper T cells named peripheral helper T (Tph) cells. Unlike T follicular helper (Tfh) cells, which interact with B cells within lymphoid organs, Tph cells provide help to B cells within inflamed tissues. Tph cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing cells. The differentiation mechanism is also partly shared between Tph and Tfh cells in humans, and both Tfh and Tph cells can be found within the same tissues, including cancer tissues. However, Tph cells display features distinct from those of Tfh cells, such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bcl-6/Blimp1 ratio. Unlike that of Tfh cells, current evidence shows that the target of Tph cells is limited to memory B cells. In this review, we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases.

A Novel Immune-Related Seventeen-Gene Signature for Predicting Early Stage Lung Squamous Cell Carcinoma Prognosis

“…Correlation analysis found that monocytes, neutrophils, NK cells resting, T cells CD4 memory resting, B cells memory, and mast cells activated were positively correlated with the risk score, and NK cells activated and T cells' follicular helper were negatively correlated with the risk score. Based on the results of the difference analysis and correlation analysis, we found that patients in the low-risk group had better long-term survival rates, which may be due to the high proportion of NK cells activated and T cells follicular helper (60)(61)(62). Most gene mutations were the initiating factor of tumorigenesis.…”

PD-1highCXCR5–CD4+ Peripheral Helper T (Tph) cells Promote Tissue-Homing Plasmablasts in COVID-19

“…Tfh cells provide essential B cell help during the adaptive immune response, and circulating Tfh (cTfh) cells share functional properties with Tfh cells 16 . Notably, PD-1 high CXCR5 − Tph cells, that are reported to be associated with extra follicular B cell differentiation 20 , were significantly increased in the blood of COVID-19 patients, in addition to significant increase in PD1 high/int CXCR5 + Tfh cells (Figure 2a, Supplemental Figure 2a, 2b). Tph cells were barely detected in healthy blood and moreover, correlated in COVID-19 patients with the frequency of circulating plasmablasts (Figure 2b, Supplemental Figure 2c) but not with clinical characteristics (age, body mass index (BMI), and sex) (Supplemental Figure 3a-c).…”

“…Our results highlight the characteristics of PD-1 high CXCR5 − Tph cells as: 1) lacking CXCR5 expression, important for the entry in GCs; 2) producing more IFNγ that is similar to T cells residing in the extra-follicular regions of lymph nodes 18 ; and 3) exhibiting highly overlapping signatures with dividing CD4 + T cells that are positively correlated with the proportion of Ki67 + plasmablasts 40 , which had lower SHM frequencies in our scRNA-seq data. These findings suggest that circulating PD-1 high CXCR5 − Tph cells may be the counterpart of T cells which promote more extra-follicular responses 20 . On the other hand, we could detect these T cells in peripheral blood of stable COVID-19 patients despite the lack of extrafollicular signatures in such patients.…”

“…To examine the mechanism of T cell regulation of plasmablast differentiation in COVID-19, we investigated the characteristics of B and T cells in patients by single cell RNA-seq (scRNA-seq) and flow cytometry datasets. Here, we report that PD-1 high CXCR5 − CD4 + T cells, so called peripheral helper T (Tph) cells 19,20 , are significantly increased and positively correlated with the frequency of plasmablasts in peripheral blood in patients with COVID-19. These Tph cells exhibit “B cell help” signatures to a similar degree as cTfh cells, but also express more inflammatory chemokine receptors including CCR2 and CCR5.…”

TFH cells in systemic sclerosis

“…Recently, another T cell subset sharing many common features with Tfh cells has been identified in several autoimmune diseases. These CXCR5 − CD4 + ICOS + CD40L + T cells named T peripheral helper (Tph) cell are also able to help B cells and have been observed in inflamed tissue in autoimmune diseases [ 17 ]. Tph cells seem to be increased in systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) peripheral blood [ 18 ].…”