Profiling circulating T follicular helper cells and their effects on B cells in post-cardiac transplant recipients
Yixuan Wang1, Zongtao Liu1, Jie Wu1
1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Circulating T follicular helper (cTfh) cells increase in heart transplant recipients, driving B cell responses and potentially long-term immune rejection. These findings highlight cTfh cells as key players in chronic immune injury post-transplantation.
Area of Science:
- Immunology
- Transplantation Immunology
Background:
- Heart transplantation recipients can experience chronic immune injury.
- Circulating T follicular helper (cTfh) cells play a role in immune responses.
- Understanding cTfh cell function is crucial for managing post-transplant complications.
Purpose of the Study:
- To evaluate circulating T follicular helper (cTfh) cells in chronic-phase heart transplant recipients.
- To characterize the function of cTfh cells in this patient population.
- To investigate the association between cTfh cells and B cell responses.
Main Methods:
- Flow cytometry was used to measure cTfh and B cell subsets in healthy controls, pre-transplant patients, and 1-year post-transplant recipients.
- In vitro co-culture experiments assessed the interaction between cTfh cells and B cells.
- ELISA quantified plasma levels of IL-21, CXCL13, IgG1, and IgG3.
Main Results:
- Chronic-phase recipients showed increased cTfh cells, PD-1+ cTfh cells, and a higher cTfh17/cTfh ratio compared to controls.
- cTfh cells promoted B cell differentiation into plasmablasts and were correlated with increased class-switched memory B cells and IgG production.
- Elevated plasma levels of IL-21 and CXCL13 were observed in chronic-phase recipients.
Conclusions:
- The proportion of cTfh cells increases during the chronic phase after heart transplantation, enhancing B cell responses.
- Soluble factors CXCL13 and IL-21, regulated by cTfh cells, may contribute to the immunopathogenesis of chronic immune injury.
- cTfh cells are implicated in driving long-term immune rejection in heart transplant recipients.
Background:
To evaluate circulating T follicular helper (cTfh) cells and characterize their function in chronic-phase recipients after heart transplantation.
Methods:
Participants were divided into healthy control (HC, n=40), preoperative (Pre, n=40), and post-transplantation chronic-phase recipient (1-year, n=40) groups. The percentages of cTfh cell subsets and CD19+ B cell subsets were measured using flow cytometry. In vitro co-culture experiments were performed using cTfh cells and B cells isolated by fluorescence-activated cell sorting. Plasma concentrations of IL-21, chemokine ligand 13 (CXCL13), immunoglobulin G1 (IgG1), and immunoglobulin G3 (IgG3) were quantified using enzyme-linked immunosorbent assays (ELISA).
Results:
cTfh and programmed cell death protein 1-positive (PD-1+) cTfh cells, the cTfh17/cTfh ratio, and class-switched memory B cells in peripheral blood were significantly increased in the 1-year group versus the HC and Pre groups (P<0.01), whereas the cTfh1/cTfh ratio and number of naïve B cells were significantly decreased in the 1-year group. Co-culture experiments showed that cTfh cells promoted B cell differentiation to plasmablasts. In the 1-year group, cTfh and PD-1+ cTfh cell numbers were positively correlated with plasmablasts in CD19+ B cells (P<0.01). The cTfh17/cTfh ratio was positively correlated with IgG3 concentrations in plasma (P<0.01). The plasma concentrations of interleukin-21 (IL-21) and CXCL13 in the 1-year group were increased compared to the HC and Pre groups (P<0.05). Chronic-phase recipients had increased proportions of CD4+CXCR5+ and CD4+CXCR5+PD-1+ cTfh cells, with a cTfh1-to-cTfh17 subtype conversion. An increased number of cTfh cells was positively correlated with B cell differentiation to plasmablasts, class-switched memory B cells, and greater IgG production.
Conclusions:
During the chronic phase, the proportion of cTfh cells increased and enhanced B cell responses. The cTfh-related soluble factors CXCL13 and IL-21 may regulate the immunopathogenesis of chronic immune injury. Thus, cTfh cells may drive long-term immune rejection in chronic-phase recipients after heart transplantation.
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