follicular helper
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2022 ◽  
Vol 74 ◽  
pp. 133-139
Uthaman Gowthaman ◽  
Suchandan Sikder ◽  
Donguk Lee ◽  
Courtney Fisher

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Feargal J. Ryan ◽  
Christopher M. Hope ◽  
Makutiro G. Masavuli ◽  
Miriam A. Lynn ◽  
Zelalem A. Mekonnen ◽  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. Methods We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection. Results Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. Conclusions Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

2022 ◽  
Vol 7 (67) ◽  
Owen Jensen ◽  
Shubhanshi Trivedi ◽  
Jeremy D. Meier ◽  
Keke C. Fairfax ◽  
J. Scott Hale ◽  

We identify a MAIT cell subset expressing T follicular helper markers and show the ability of MAIT cells to support B cell responses in the mucosa.

Pathobiology ◽  
2022 ◽  
pp. 1-11
Omar Bushara ◽  
David Joseph Escobar ◽  
Samuel Edward Weinberg ◽  
Leyu Sun ◽  
Jie Liao ◽  

<b><i>Background:</i></b> Crohn’s disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. <b><i>Summary:</i></b> Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.

2022 ◽  
Vol 12 ◽  
Hugo Barcenilla ◽  
Mikael Pihl ◽  
Jeanette Wahlberg ◽  
Johnny Ludvigsson ◽  
Rosaura Casas

Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.

2022 ◽  
Kara A. O’Neal ◽  
Leah E. Latham ◽  
Enatha Ntirandekura ◽  
Camille L. Foscue ◽  
Jason S. Stumhofer

Inducible T cell co-stimulator (ICOS) plays a key role in the differentiation and maintenance of follicular helper T (Tfh) cells and thus germinal center (GC) formation. Previously, our lab showed in a Plasmodium chabaudi infection model that Icos -/- mice were significantly impaired in their ability to form GCs despite a persistent infection and thus a continued antigen (Ag) load. Here, we show that resolution of a primary infection with P. yoelii , was delayed in Icos -/- mice. This phenotype was associated with a reduction in the accumulation of Tfh-like and GC Tfh cells and an early deficiency in Ag-specific antibody (Ab) production. However, Icos -/- mice could form GCs, though they were less frequent in number than in wild-type (WT) mice. Nonetheless, the Ag-specific Abs from Icos -/- mice lacked signs of affinity maturation, suggesting functional defects associated with these GCs. Eventually, these GC structures dissipated more rapidly in Icos -/- mice than in WT mice. Moreover, the ability of Icos -/- mice to form these GC structures is not reliant on the high Ag load associated with P. yoelii infections, as GC formation was preserved in Icos -/- mice treated with atovaquone. Finally, mice were unable to form secondary GCs in the absence of ICOS after re-challenge. Overall, these data demonstrate the necessity of ICOS in the maintenance of Tfh cells, the formation and maintenance of sufficient numbers of functioning GCs, and the ability to generate new GC structures after re-infection with P. yoelii .

2022 ◽  
pp. 7-11
Tadaaki Inano ◽  
Hajime Yasuda ◽  
Yutaka Tsukune ◽  
Miyuki Tsutsui ◽  
Nadila Wali ◽  

TAFRO syndrome is a relatively new disease entity first reported in 2010. We report a case of TAFRO syndrome accommodated by abnormal exacerbation of moderately differentiated gastric adenocarcinoma. The pathophysiology of TAFRO syndrome is largely unknown, but because the disease often responds to immunosuppressive therapy and also because T follicular helper (Tfh) cells are reported to be drastically decreased in TAFRO syndrome, involvement of a dysregulated immune system can be speculated. Growing evidence points toward a pivotal role of Tfh cells in tumor immunity through supporting ectopic lymphoid structures, which are recruitment sites for cells directly engaging in antitumor activity such as CD8<sup>+</sup> T cells, NK cells, and macrophages. In fact, Tfh cells are reported to positively correlate with longer survival in human colorectal and breast cancer. Combined with our observations of hyperprogressive gastric cancer in the presented patient, an impaired tumor immunity is strongly indicated in TAFRO syndrome.

2022 ◽  
Vol 12 ◽  
Yi Chen ◽  
Shuwen You ◽  
Jie Li ◽  
Yifan Zhang ◽  
Georgia Kokaraki ◽  

Despite the fact that management of EC is moving towards four TCGA-based molecular classifications, a pronounced variation in immune response among these molecular subtypes limits its clinical use. We aimed to investigate the determinant biomarker of ICI response in endometrial cancer (EC). We characterized transcriptome signatures associated with tumor immune microenvironment in EC. Two immune infiltration signatures were identified from the TCGA database (n = 520). The high- and low-infiltration clusters were compared for differences in patient clinical characteristics, genomic features, and immune cell transcription signatures for ICI prediction. A Lasso Cox regression model was applied to construct a prognostic gene signature. Time-dependent receiver operating characteristic curve, Kaplan–Meier curve, nomogram, and decision curve analyses were used to assess the prediction capacity. The efficacy of potential biomarker was validated by the Karolinska endometrial cancer cohort (n = 260). Immune signature profiling suggested that T follicular helper–like cells (Tfh) may be an important and favorable factor for EC; high Tfh infiltration showed potential for clinical use in the anti-PD-1 treatment. A Tfh Infiltration Risk Model (TIRM) established using eight genes was validated, and it outperformed the Immune Infiltration Risk Model. The TIRM had a stable prognostic value in combination with clinical risk factors and could be considered as a valuable tool in a clinical prediction model. We identified CRABP1 as an individual poor prognostic factor in EC. The Tfh-based classification distinguishes immune characteristics and predicts ICI efficacy. A nomogram based on Tfh-related risk score accurately predicted the prognosis of patients with EC, demonstrating superior performance to TCGA-based classification.

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